Publications
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141.
Berbeco, R; Korideck, H; Ngwa, W; Kumar, R; Patel, J; Sridhar, S; Johnson, S; Price, B; Kimmelman, A; Makrigiorgos, M
TU-C-BRB-11: In Vitro Dose Enhancement from Gold Nanoparticles under Different Clinical MV Photon Beam Configurations Journal Article
In: Medical Physics, vol. 39, no. 6Part23, pp. 3900–3901, 2012.
@article{berbeco2012tu,
title = {TU-C-BRB-11: In Vitro Dose Enhancement from Gold Nanoparticles under Different Clinical MV Photon Beam Configurations},
author = {R Berbeco and H Korideck and W Ngwa and R Kumar and J Patel and S Sridhar and S Johnson and B Price and A Kimmelman and M Makrigiorgos},
year = {2012},
date = {2012-01-01},
journal = {Medical Physics},
volume = {39},
number = {6Part23},
pages = {3900--3901},
publisher = {American Association of Physicists in Medicine},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
142.
Ngwa, W; Korideck, H; Kimmelman, A; Kassis, AI; Kumar, R; Sridhar, S; Makrigiorgos, M; Cormack, RA
In vitro dose enhancement from gold nanoparticles during low-dose-rate gamma irradiation with I-125 brachytherapy seeds Journal Article
In: International Journal of Radiation Oncology• Biology• Physics, vol. 84, no. 3, pp. S134, 2012.
@article{ngwa2012vitro,
title = {In vitro dose enhancement from gold nanoparticles during low-dose-rate gamma irradiation with I-125 brachytherapy seeds},
author = {W Ngwa and H Korideck and A Kimmelman and AI Kassis and R Kumar and S Sridhar and M Makrigiorgos and RA Cormack},
year = {2012},
date = {2012-01-01},
journal = {International Journal of Radiation Oncology• Biology• Physics},
volume = {84},
number = {3},
pages = {S134},
publisher = {Elsevier},
abstract = {Purpose/Objective(s)
Recent studies have predicted substantial dose enhancement to tumors when gold nanoparticles (AuNP) are employed as adjuvants to radiation therapy at kV energies. Because the enhancement results from processes at kV energies, some studies proposed gold nanoparticle-aided brachytherapy as a radiation therapy approach with potential to meet technical and clinical requirements for implementation. To the best of our knowledge, there has been no study providing clear experimental evidence to corroborate the substantial dose enhancement predictions when irradiating with low dose rate gamma photons from brachytherapy sources. This study investigates the in vitro dose enhancement of AuNP during irradiation of cancer cells by I-125 low dose rate brachytherapy sources.
Materials/Methods
HeLa cell cultures were incubated with and without gold nanoparticles (AuNP) in alternate wells of an 8 well-chamber slide; 4 wells on each slide had cell cultures with AuNP while 4 wells contained cell cultures with no AuNP. Two slides were prepared for each experiment: one slide to be irradiated while the other serves as sham-irradiation control. The cells were irradiated with gamma photons from I-125 brachytherapy seeds in a plaque contained in a custom-built irradiation jig. The plaque was designed to achieve a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at 370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose rates were varied by varying the height of the cell culture slide above the plaque containing the I-125 seeds. Residual gammaH2AX was measured 24 hours after irradiation and used to compare the dose response of the cells with and without AuNP. In addition, the relative dose enhancement factor (DEF), representing the ratio of the dose to the cells with and without the presence of AuNP, was estimated from the data.
Results
From the dose response behavior, the results show that the biologic effect when irradiating with 0.2 mg/mL concentration of AuNP is up to 2.3 times greater than without AuNP. This major increase in radiation damage to cancer cells incubated with AuNP corresponds to an estimated DEF of over 3.5.
Conclusions
Our findings provide the first experimental evidence of substantial dose enhancement from gold nanoparticles during low dose rate gamma irradiation from brachytherapy sources. These in vitro study results provide impetus for further preclinical and clinical investigations in the development of gold nanoparticle-aided brachytherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose/Objective(s)
Recent studies have predicted substantial dose enhancement to tumors when gold nanoparticles (AuNP) are employed as adjuvants to radiation therapy at kV energies. Because the enhancement results from processes at kV energies, some studies proposed gold nanoparticle-aided brachytherapy as a radiation therapy approach with potential to meet technical and clinical requirements for implementation. To the best of our knowledge, there has been no study providing clear experimental evidence to corroborate the substantial dose enhancement predictions when irradiating with low dose rate gamma photons from brachytherapy sources. This study investigates the in vitro dose enhancement of AuNP during irradiation of cancer cells by I-125 low dose rate brachytherapy sources.
Materials/Methods
HeLa cell cultures were incubated with and without gold nanoparticles (AuNP) in alternate wells of an 8 well-chamber slide; 4 wells on each slide had cell cultures with AuNP while 4 wells contained cell cultures with no AuNP. Two slides were prepared for each experiment: one slide to be irradiated while the other serves as sham-irradiation control. The cells were irradiated with gamma photons from I-125 brachytherapy seeds in a plaque contained in a custom-built irradiation jig. The plaque was designed to achieve a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at 370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose rates were varied by varying the height of the cell culture slide above the plaque containing the I-125 seeds. Residual gammaH2AX was measured 24 hours after irradiation and used to compare the dose response of the cells with and without AuNP. In addition, the relative dose enhancement factor (DEF), representing the ratio of the dose to the cells with and without the presence of AuNP, was estimated from the data.
Results
From the dose response behavior, the results show that the biologic effect when irradiating with 0.2 mg/mL concentration of AuNP is up to 2.3 times greater than without AuNP. This major increase in radiation damage to cancer cells incubated with AuNP corresponds to an estimated DEF of over 3.5.
Conclusions
Our findings provide the first experimental evidence of substantial dose enhancement from gold nanoparticles during low dose rate gamma irradiation from brachytherapy sources. These in vitro study results provide impetus for further preclinical and clinical investigations in the development of gold nanoparticle-aided brachytherapy.
Recent studies have predicted substantial dose enhancement to tumors when gold nanoparticles (AuNP) are employed as adjuvants to radiation therapy at kV energies. Because the enhancement results from processes at kV energies, some studies proposed gold nanoparticle-aided brachytherapy as a radiation therapy approach with potential to meet technical and clinical requirements for implementation. To the best of our knowledge, there has been no study providing clear experimental evidence to corroborate the substantial dose enhancement predictions when irradiating with low dose rate gamma photons from brachytherapy sources. This study investigates the in vitro dose enhancement of AuNP during irradiation of cancer cells by I-125 low dose rate brachytherapy sources.
Materials/Methods
HeLa cell cultures were incubated with and without gold nanoparticles (AuNP) in alternate wells of an 8 well-chamber slide; 4 wells on each slide had cell cultures with AuNP while 4 wells contained cell cultures with no AuNP. Two slides were prepared for each experiment: one slide to be irradiated while the other serves as sham-irradiation control. The cells were irradiated with gamma photons from I-125 brachytherapy seeds in a plaque contained in a custom-built irradiation jig. The plaque was designed to achieve a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at 370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose rates were varied by varying the height of the cell culture slide above the plaque containing the I-125 seeds. Residual gammaH2AX was measured 24 hours after irradiation and used to compare the dose response of the cells with and without AuNP. In addition, the relative dose enhancement factor (DEF), representing the ratio of the dose to the cells with and without the presence of AuNP, was estimated from the data.
Results
From the dose response behavior, the results show that the biologic effect when irradiating with 0.2 mg/mL concentration of AuNP is up to 2.3 times greater than without AuNP. This major increase in radiation damage to cancer cells incubated with AuNP corresponds to an estimated DEF of over 3.5.
Conclusions
Our findings provide the first experimental evidence of substantial dose enhancement from gold nanoparticles during low dose rate gamma irradiation from brachytherapy sources. These in vitro study results provide impetus for further preclinical and clinical investigations in the development of gold nanoparticle-aided brachytherapy.
143.
Cormack, R; Nguyen, P; D'Amico, AV; Sridhar, S; Makrigiorgos, GM
Locally Drug Enhanced Brachytherapy: A Comparison of 2 Approaches Based on Biologically Effective Dose Journal Article
In: International Journal of Radiation Oncology• Biology• Physics, vol. 84, no. 3, pp. S854–S855, 2012.
@article{cormack2012locally,
title = {Locally Drug Enhanced Brachytherapy: A Comparison of 2 Approaches Based on Biologically Effective Dose},
author = {R Cormack and P Nguyen and AV D'Amico and S Sridhar and GM Makrigiorgos},
year = {2012},
date = {2012-01-01},
journal = {International Journal of Radiation Oncology• Biology• Physics},
volume = {84},
number = {3},
pages = {S854--S855},
publisher = {Elsevier},
abstract = {Purpose/Objective(s)
Permanent prostate brachytherapy may be enhanced by delivering radiosensitizer to the target during the implant process. Nanoparticles released from a substrate can deliver drug over an extended period of time and can be engineered to adjust their diffusion parameters. Nanoparticle eluting polymers have been proposed to coat radioactive sources or to form brachytherapy spacers as a way of delivering drug to the prostate. This work determines whether it is preferable to deliver radiosensitizer from sources or spacers.
Materials/Methods
The relative effectiveness of spacers or sources as sources of sensitizer was evaluated by comparing biologic effective dose (BED) of the combined effect of radiation and drug distributions within the prostate. Treatment plans of six patients receiving 125I prostate implants were analyzed under an IRB approved protocol. Target contours were extracted as were the locations of radioactive sources and spacers. Radiation dose was calculated according to AAPM TG43 methodology. Drug distributions were calculated from a solution of the diffusion equation, relative to the steady state concentration at the eluter's surface, for a range of diffusion-elimination modulus (φb) values and concentration needed for maximum sensitization (Cs). φb is viewed as a variable because the properties of the nanoparticles can be adjusted to affect diffusion and time of residence. Cs is treated as a variable because the amplitude of the drug distribution depends on the capacity of the implanted object and the time frame of release. BED calculations of the composite effect were done. The calculations were compared to an approach where the location of the spacers was allowed to be adjusted.
Results
The ratio of the BED for the two delivery approaches is presented in the 2D parameter space of φb and Cs. A full sensitization region, corresponding to low values of φb and Cs, shows no difference between approaches. The majority of the remaining parameter space, showed that using spacers to radiosensitize results in a greater BED. Changing the spacer locations from fixed by the treatment plan to adjustable allowed further increase of BED.
Conclusions
Using brachytherapy spacers as a vehicle to deliver radiosensitizing nanoparticles offers a greater potential to increase the effectiveness of prostate brachytherapy by in-situ radiosensitization. Further increase was achieved by treating spacer location as planning parameter. Using implanted non-radioactive devices for local radiosensitization suggests the potential of planned chemical distributions in conjunction with radiation planning to produce an optimal combined result.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose/Objective(s)
Permanent prostate brachytherapy may be enhanced by delivering radiosensitizer to the target during the implant process. Nanoparticles released from a substrate can deliver drug over an extended period of time and can be engineered to adjust their diffusion parameters. Nanoparticle eluting polymers have been proposed to coat radioactive sources or to form brachytherapy spacers as a way of delivering drug to the prostate. This work determines whether it is preferable to deliver radiosensitizer from sources or spacers.
Materials/Methods
The relative effectiveness of spacers or sources as sources of sensitizer was evaluated by comparing biologic effective dose (BED) of the combined effect of radiation and drug distributions within the prostate. Treatment plans of six patients receiving 125I prostate implants were analyzed under an IRB approved protocol. Target contours were extracted as were the locations of radioactive sources and spacers. Radiation dose was calculated according to AAPM TG43 methodology. Drug distributions were calculated from a solution of the diffusion equation, relative to the steady state concentration at the eluter's surface, for a range of diffusion-elimination modulus (φb) values and concentration needed for maximum sensitization (Cs). φb is viewed as a variable because the properties of the nanoparticles can be adjusted to affect diffusion and time of residence. Cs is treated as a variable because the amplitude of the drug distribution depends on the capacity of the implanted object and the time frame of release. BED calculations of the composite effect were done. The calculations were compared to an approach where the location of the spacers was allowed to be adjusted.
Results
The ratio of the BED for the two delivery approaches is presented in the 2D parameter space of φb and Cs. A full sensitization region, corresponding to low values of φb and Cs, shows no difference between approaches. The majority of the remaining parameter space, showed that using spacers to radiosensitize results in a greater BED. Changing the spacer locations from fixed by the treatment plan to adjustable allowed further increase of BED.
Conclusions
Using brachytherapy spacers as a vehicle to deliver radiosensitizing nanoparticles offers a greater potential to increase the effectiveness of prostate brachytherapy by in-situ radiosensitization. Further increase was achieved by treating spacer location as planning parameter. Using implanted non-radioactive devices for local radiosensitization suggests the potential of planned chemical distributions in conjunction with radiation planning to produce an optimal combined result.
Permanent prostate brachytherapy may be enhanced by delivering radiosensitizer to the target during the implant process. Nanoparticles released from a substrate can deliver drug over an extended period of time and can be engineered to adjust their diffusion parameters. Nanoparticle eluting polymers have been proposed to coat radioactive sources or to form brachytherapy spacers as a way of delivering drug to the prostate. This work determines whether it is preferable to deliver radiosensitizer from sources or spacers.
Materials/Methods
The relative effectiveness of spacers or sources as sources of sensitizer was evaluated by comparing biologic effective dose (BED) of the combined effect of radiation and drug distributions within the prostate. Treatment plans of six patients receiving 125I prostate implants were analyzed under an IRB approved protocol. Target contours were extracted as were the locations of radioactive sources and spacers. Radiation dose was calculated according to AAPM TG43 methodology. Drug distributions were calculated from a solution of the diffusion equation, relative to the steady state concentration at the eluter's surface, for a range of diffusion-elimination modulus (φb) values and concentration needed for maximum sensitization (Cs). φb is viewed as a variable because the properties of the nanoparticles can be adjusted to affect diffusion and time of residence. Cs is treated as a variable because the amplitude of the drug distribution depends on the capacity of the implanted object and the time frame of release. BED calculations of the composite effect were done. The calculations were compared to an approach where the location of the spacers was allowed to be adjusted.
Results
The ratio of the BED for the two delivery approaches is presented in the 2D parameter space of φb and Cs. A full sensitization region, corresponding to low values of φb and Cs, shows no difference between approaches. The majority of the remaining parameter space, showed that using spacers to radiosensitize results in a greater BED. Changing the spacer locations from fixed by the treatment plan to adjustable allowed further increase of BED.
Conclusions
Using brachytherapy spacers as a vehicle to deliver radiosensitizing nanoparticles offers a greater potential to increase the effectiveness of prostate brachytherapy by in-situ radiosensitization. Further increase was achieved by treating spacer location as planning parameter. Using implanted non-radioactive devices for local radiosensitization suggests the potential of planned chemical distributions in conjunction with radiation planning to produce an optimal combined result.
144.
D.Plouffea, Brian; K.Nagesha, Dattatri; S.DiPietro, Robert; Sridhar, Srinvas; Heimand, Don; K.Murthya, Shashi; H.Lewisa, Lewis
Thermomagnetic determination of Fe3O4 magnetic nanoparticle diameters for biomedical applications Journal Article
In: Journal of Magnetism and Magnetic Materials, vol. 323, no. 17, pp. 2310-2317, 2011.
@article{H.Lewisa2011,
title = {Thermomagnetic determination of Fe3O4 magnetic nanoparticle diameters for biomedical applications},
author = {Brian D.Plouffea and Dattatri K.Nagesha and Robert S.DiPietro and Srinvas Sridhar and Don Heimand and Shashi K.Murthya and Lewis H.Lewisa
},
doi = {S0304885311002423},
year = {2011},
date = {2011-09-01},
journal = {Journal of Magnetism and Magnetic Materials},
volume = {323},
number = {17},
pages = {2310-2317},
abstract = {The utility and promise of magnetic nanoparticles (MagNPs) for biomedicine rely heavily on accurate determination of the particle diameter attributes. While the average functional size and size distribution of the magnetic nanoparticles directly impact the implementation and optimization of nanobiotechnology applications in which they are employed, the determination of these attributes using electron microscopy techniques can be time-consuming and misrepresentative of the full nanoparticle population. In this work the average particle diameter and distribution of an ensemble of Fe3O4 ferrimagnetic nanoparticles are determined solely from temperature-dependent magnetization measurements; the results compare favorably to those obtained from extensive electron microscopy observations. The attributes of a population of biocompatible Fe3O4 nanoparticles synthesized by a thermal decomposition method are obtained from quantitative evaluation of a model that incorporates the distribution of superparamagnetic blocking temperatures represented through thermomagnetization data. The average size and size distributions are determined from magnetization data via temperature-dependent zero-field-cooled magnetization. The current work is unique from existing approaches based on magnetic measurement for the characterization of a nanoparticle ensemble as it provides both the average particle size as well as the particle size distribution.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The utility and promise of magnetic nanoparticles (MagNPs) for biomedicine rely heavily on accurate determination of the particle diameter attributes. While the average functional size and size distribution of the magnetic nanoparticles directly impact the implementation and optimization of nanobiotechnology applications in which they are employed, the determination of these attributes using electron microscopy techniques can be time-consuming and misrepresentative of the full nanoparticle population. In this work the average particle diameter and distribution of an ensemble of Fe3O4 ferrimagnetic nanoparticles are determined solely from temperature-dependent magnetization measurements; the results compare favorably to those obtained from extensive electron microscopy observations. The attributes of a population of biocompatible Fe3O4 nanoparticles synthesized by a thermal decomposition method are obtained from quantitative evaluation of a model that incorporates the distribution of superparamagnetic blocking temperatures represented through thermomagnetization data. The average size and size distributions are determined from magnetization data via temperature-dependent zero-field-cooled magnetization. The current work is unique from existing approaches based on magnetic measurement for the characterization of a nanoparticle ensemble as it provides both the average particle size as well as the particle size distribution.
145.
Makrigiorgos, Robert A. Cormack; Paul L. Nguyen; Anthony V. D'Amico; Sri Sridhar; Mike
Optimal drug release schedule for in-situ radiosensitization of image guided permanent prostate implants Journal Article
In: Proceedings Volume 7964, Medical Imaging 2011: Visualization, Image-Guided Procedures, and Modeling, vol. 7964, no. 2011, 2011.
@article{Makrigiorgos2011,
title = {Optimal drug release schedule for in-situ radiosensitization of image guided permanent prostate implants},
author = {Robert A. Cormack; Paul L. Nguyen; Anthony V. D'Amico; Sri Sridhar; Mike Makrigiorgos
},
doi = {10.1117/12.878139},
year = {2011},
date = {2011-03-03},
journal = {Proceedings Volume 7964, Medical Imaging 2011: Visualization, Image-Guided Procedures, and Modeling},
volume = {7964},
number = {2011},
abstract = {Planned in-situ radiosensitization may improve the therapeutic ratio of image guided 125I prostate brachytherapy. Spacers used in permanent implants may be manufactured from a radiosensitizer-releasing polymer to deliver protracted localized sensitization of the prostate. Such devices will have a limited drug-loading capacity, and the drug release schedule that optimizes outcome, under such a constraint, is not known. This work determines the optimal elution schedules for 125I prostate brachytherapy. The interaction between brachytherapy dose distributions and drug distribution around drug eluting spacers is modeled using a linear-quadratic (LQ) model of cell kill. Clinical brachytherapy plans were used to calculate the biologic effective dose (BED) for planned radiation dose distributions while adding the spatial distributions of radiosensitizer while varying the temporal release schedule subject to a constraint on the drug capacity of the eluting spacers. Results: The greatest increase in BED is achieved by schedules with the greatest sensitization early in the implant. Making brachytherapy spacers from radiosensitizer eluting polymer transforms inert parts of the implant process into a means of enhancing the effect of the brachytherapy radiation. Such an approach may increase the therapeutic ratio of prostate brachytherapy or offer a means of locally boosting the radiation effect without increasing the radiation dose to surrounding tissues.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Planned in-situ radiosensitization may improve the therapeutic ratio of image guided 125I prostate brachytherapy. Spacers used in permanent implants may be manufactured from a radiosensitizer-releasing polymer to deliver protracted localized sensitization of the prostate. Such devices will have a limited drug-loading capacity, and the drug release schedule that optimizes outcome, under such a constraint, is not known. This work determines the optimal elution schedules for 125I prostate brachytherapy. The interaction between brachytherapy dose distributions and drug distribution around drug eluting spacers is modeled using a linear-quadratic (LQ) model of cell kill. Clinical brachytherapy plans were used to calculate the biologic effective dose (BED) for planned radiation dose distributions while adding the spatial distributions of radiosensitizer while varying the temporal release schedule subject to a constraint on the drug capacity of the eluting spacers. Results: The greatest increase in BED is achieved by schedules with the greatest sensitization early in the implant. Making brachytherapy spacers from radiosensitizer eluting polymer transforms inert parts of the implant process into a means of enhancing the effect of the brachytherapy radiation. Such an approach may increase the therapeutic ratio of prostate brachytherapy or offer a means of locally boosting the radiation effect without increasing the radiation dose to surrounding tissues.
146.
Alvarado-Velez, Melissa; Rivera-Chacon, Delva M; Acevedo-Morantes, Claudia Y; Menon, Latika; Nagesha, Dattatri; Gultepe, Evin; Sridhar, Srinivas; Ramirez-Vick, Jaime E; Singh, Surinder P
Effects of fibronectin and vitronectin on human fetal osteoblast cell attachment and proliferation on nanostructured titania surfaces Proceedings Article
In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC 1155 16TH ST, NW, WASHINGTON, DC 20036 USA 2011.
@inproceedings{alvarado2011effects,
title = {Effects of fibronectin and vitronectin on human fetal osteoblast cell attachment and proliferation on nanostructured titania surfaces},
author = {Melissa Alvarado-Velez and Delva M Rivera-Chacon and Claudia Y Acevedo-Morantes and Latika Menon and Dattatri Nagesha and Evin Gultepe and Srinivas Sridhar and Jaime E Ramirez-Vick and Surinder P Singh},
year = {2011},
date = {2011-01-01},
booktitle = {ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY},
volume = {241},
organization = {AMER CHEMICAL SOC 1155 16TH ST, NW, WASHINGTON, DC 20036 USA},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
147.
Sridhar, Srinivas; Nagesha, Dattatri; Tada, Dayane; Kumar, Rajiv; Makrigiorgos, Mike G; Cormack, Robert
Radio-sensitizer eluting nanoporous coatings on fiducials markers: Biological in-situ dose-painting for IGRT Miscellaneous
2011.
@misc{sridhar2011radio,
title = {Radio-sensitizer eluting nanoporous coatings on fiducials markers: Biological in-situ dose-painting for IGRT},
author = {Srinivas Sridhar and Dattatri Nagesha and Dayane Tada and Rajiv Kumar and Mike G Makrigiorgos and Robert Cormack},
year = {2011},
date = {2011-01-01},
publisher = {American Association for Cancer Research},
abstract = {Image-guided radiation treatments routinely utilize implantable devices, such as radio-opaque fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) using local delivery of radiosensitizers embedded within nanoparticles and nanoporous polymer matrices coating gold fiducial markers. Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed the controlled release of the molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Coumarin-6, a model for a fluorescent hydrophobic drug, in a chitosan matrix applied as fiducial coating. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. For flat gold films and gold fiducials coated with Doxorubicin in PMMA matrix, an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin-6 loaded nanoparticles from chitosan film on gold fiducials showed a continuous release of NPs from the coating during forty days. (63±10)% of NPs were released in twenty days. After that, the release became slower and additional 37% of release was observed after twenty-days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Results show that dosage and rate of release of these radiosensitizers can be precisely tailored to achieve the desired release profile for BIS-IGRT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674
©2011 American Association for Cancer Research},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Image-guided radiation treatments routinely utilize implantable devices, such as radio-opaque fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) using local delivery of radiosensitizers embedded within nanoparticles and nanoporous polymer matrices coating gold fiducial markers. Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed the controlled release of the molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Coumarin-6, a model for a fluorescent hydrophobic drug, in a chitosan matrix applied as fiducial coating. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. For flat gold films and gold fiducials coated with Doxorubicin in PMMA matrix, an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin-6 loaded nanoparticles from chitosan film on gold fiducials showed a continuous release of NPs from the coating during forty days. (63±10)% of NPs were released in twenty days. After that, the release became slower and additional 37% of release was observed after twenty-days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Results show that dosage and rate of release of these radiosensitizers can be precisely tailored to achieve the desired release profile for BIS-IGRT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674
©2011 American Association for Cancer Research
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674
©2011 American Association for Cancer Research
148.
Gultepe, Evin; Nagesha, Dattatri; Sridhar, Srinivas; Amiji, Mansoor
Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices Journal Article
In: Advanced drug delivery reviews, vol. 62, no. 3, pp. 305–315, 2010.
@article{gultepe2010nanoporous,
title = {Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices},
author = {Evin Gultepe and Dattatri Nagesha and Srinivas Sridhar and Mansoor Amiji},
year = {2010},
date = {2010-01-01},
journal = {Advanced drug delivery reviews},
volume = {62},
number = {3},
pages = {305--315},
publisher = {Elsevier},
abstract = {The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al2O3), titanium oxide (TiO2) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution pro?les of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release pro?les extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved ef?cacy and integration of implants in a variety of therapeutic situations.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al2O3), titanium oxide (TiO2) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution pro?les of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release pro?les extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved ef?cacy and integration of implants in a variety of therapeutic situations.
149.
Stambaugh, C; Tada, D; Nagesha, D; Jost, E; Levy, C; Cormack, RA; Makrigiorgos, M; Sridhar, S
WE-E-204B-02: Release Kinetics of Radio-Sensitizers from Nanoporous Coatings on Gold Fiducials: Biological In-Situ Dose-Painting for IGRT Journal Article
In: Medical Physics, vol. 37, no. 6Part13, pp. 3437–3438, 2010.
@article{stambaugh2010we,
title = {WE-E-204B-02: Release Kinetics of Radio-Sensitizers from Nanoporous Coatings on Gold Fiducials: Biological In-Situ Dose-Painting for IGRT},
author = {C Stambaugh and D Tada and D Nagesha and E Jost and C Levy and RA Cormack and M Makrigiorgos and S Sridhar},
year = {2010},
date = {2010-01-01},
journal = {Medical Physics},
volume = {37},
number = {6Part13},
pages = {3437--3438},
publisher = {American Association of Physicists in Medicine},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
150.
Cormack, Robert A; Nagesha, Dattatri; Gultepe, Evin; Nguyen, Paul; D'Amico, Anthony V; Sridhar, Srinivas; Makrigiorgos, Mike
Drug Eluting Brachytherapy Spacers: A Potential for Biologically-Enhanced Brachytherapy Journal Article
In: Brachytherapy, vol. 9, pp. S48–S49, 2010.
@article{cormack2010drug,
title = {Drug Eluting Brachytherapy Spacers: A Potential for Biologically-Enhanced Brachytherapy},
author = {Robert A Cormack and Dattatri Nagesha and Evin Gultepe and Paul Nguyen and Anthony V D'Amico and Srinivas Sridhar and Mike Makrigiorgos},
year = {2010},
date = {2010-01-01},
journal = {Brachytherapy},
volume = {9},
pages = {S48--S49},
publisher = {Elsevier},
abstract = {Purpose: Ultrasound-guided prostate brachytherapy routinely implants spacers between the 125I radiation sources, that provide no therapeutic benefit although they are essential to the technical completion of the implant. The spacers offer a vehicle for in-situ delivery of radio-sensitizer, or other agents, which could increase the biologic effective dose of the radiation. This work studies the achievable drug coverage as a function of the chemical and physical properties of the drugs and devices.
Materials and Methods: Fluorescent doxorubicin in a polymer suspension and gold substrate were used to evaluate the ability to create a radio-opaque drug eluter. Elution kinetics from polymer coating of gold substrate was measured via fluorescence spectrometry. An analytic solution to the diffusion elimination equation was used to perform computer modeling of drug distributions produced by configurations of eluters placed within ultrasound guided prostate implants. Measures of tumor coverage and normal tissue involvement are evaluated for multiple combinations of eluter sizes and diffusion elimination moduli φb.
Results: Timed-release of doxorubicin from a polymer coating on a gold substrate, as shown in the top half of the figure, is technically possible. The many spacers used in prostate brachytherapy are sufficient to sensitize a portion of the prostate with values of φb close to the calculated ones. The use of drug-eluting brachytherapy spacers would enable a more localized enhancement in biologic effective dose than what can be delivered by a local brachytherapy boost. The bottom half of the figure shows a prostate implant at treated at our institution and and how it could be locally enhanced with the addition of a small number of drug eluting spacers.
Conclusions: IGRT techniques, such as ultrasound-guided brachytherapy, already implant devices within tumors as part of the standard of care. These devices may be enhanced with drug-eluting coatings to provide an in-situ increase in biologic effective dose without increasing the physical dose involved in the therapy. Generalization of this biologically in-situ enhanced IGRT (BIS-IGRT) to other agents in combination with advances in biologic imaging may provide an opportunity for personalized biologically in-situ enhanced brachytherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose: Ultrasound-guided prostate brachytherapy routinely implants spacers between the 125I radiation sources, that provide no therapeutic benefit although they are essential to the technical completion of the implant. The spacers offer a vehicle for in-situ delivery of radio-sensitizer, or other agents, which could increase the biologic effective dose of the radiation. This work studies the achievable drug coverage as a function of the chemical and physical properties of the drugs and devices.
Materials and Methods: Fluorescent doxorubicin in a polymer suspension and gold substrate were used to evaluate the ability to create a radio-opaque drug eluter. Elution kinetics from polymer coating of gold substrate was measured via fluorescence spectrometry. An analytic solution to the diffusion elimination equation was used to perform computer modeling of drug distributions produced by configurations of eluters placed within ultrasound guided prostate implants. Measures of tumor coverage and normal tissue involvement are evaluated for multiple combinations of eluter sizes and diffusion elimination moduli φb.
Results: Timed-release of doxorubicin from a polymer coating on a gold substrate, as shown in the top half of the figure, is technically possible. The many spacers used in prostate brachytherapy are sufficient to sensitize a portion of the prostate with values of φb close to the calculated ones. The use of drug-eluting brachytherapy spacers would enable a more localized enhancement in biologic effective dose than what can be delivered by a local brachytherapy boost. The bottom half of the figure shows a prostate implant at treated at our institution and and how it could be locally enhanced with the addition of a small number of drug eluting spacers.
Conclusions: IGRT techniques, such as ultrasound-guided brachytherapy, already implant devices within tumors as part of the standard of care. These devices may be enhanced with drug-eluting coatings to provide an in-situ increase in biologic effective dose without increasing the physical dose involved in the therapy. Generalization of this biologically in-situ enhanced IGRT (BIS-IGRT) to other agents in combination with advances in biologic imaging may provide an opportunity for personalized biologically in-situ enhanced brachytherapy.
Materials and Methods: Fluorescent doxorubicin in a polymer suspension and gold substrate were used to evaluate the ability to create a radio-opaque drug eluter. Elution kinetics from polymer coating of gold substrate was measured via fluorescence spectrometry. An analytic solution to the diffusion elimination equation was used to perform computer modeling of drug distributions produced by configurations of eluters placed within ultrasound guided prostate implants. Measures of tumor coverage and normal tissue involvement are evaluated for multiple combinations of eluter sizes and diffusion elimination moduli φb.
Results: Timed-release of doxorubicin from a polymer coating on a gold substrate, as shown in the top half of the figure, is technically possible. The many spacers used in prostate brachytherapy are sufficient to sensitize a portion of the prostate with values of φb close to the calculated ones. The use of drug-eluting brachytherapy spacers would enable a more localized enhancement in biologic effective dose than what can be delivered by a local brachytherapy boost. The bottom half of the figure shows a prostate implant at treated at our institution and and how it could be locally enhanced with the addition of a small number of drug eluting spacers.
Conclusions: IGRT techniques, such as ultrasound-guided brachytherapy, already implant devices within tumors as part of the standard of care. These devices may be enhanced with drug-eluting coatings to provide an in-situ increase in biologic effective dose without increasing the physical dose involved in the therapy. Generalization of this biologically in-situ enhanced IGRT (BIS-IGRT) to other agents in combination with advances in biologic imaging may provide an opportunity for personalized biologically in-situ enhanced brachytherapy.
151.
Gultepe, Evin; Reynoso, Francisco J; Jhaveri, Aditi; Kulkarni, Praveen; Nagesha, Dattatri; Ferris, Craig; Harisinghani, Mukesh; Campbell, Robert B; Sridhar, Srinivas
Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution Journal Article
In: Nanomedicine, vol. 5, no. 8, pp. 1173–1182, 2010.
@article{gultepe2010monitoring,
title = {Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution},
author = {Evin Gultepe and Francisco J Reynoso and Aditi Jhaveri and Praveen Kulkarni and Dattatri Nagesha and Craig Ferris and Mukesh Harisinghani and Robert B Campbell and Srinivas Sridhar},
year = {2010},
date = {2010-01-01},
journal = {Nanomedicine},
volume = {5},
number = {8},
pages = {1173--1182},
publisher = {Future Medicine Ltd London, UK},
abstract = {The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. We have shown that tumor signal intensities in T2-weighted MR images decreased by an average of 20 ± 5% and T2* relaxation times decreased by 14 ± 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 ± 12% and a T2* relaxation time decrease of 27 ± 8 ms after the same time period with the aid of magnetic guidance. MR and biodistribution analysis clearly show the ef?cacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. We have shown that tumor signal intensities in T2-weighted MR images decreased by an average of 20 ± 5% and T2* relaxation times decreased by 14 ± 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 ± 12% and a T2* relaxation time decrease of 27 ± 8 ms after the same time period with the aid of magnetic guidance. MR and biodistribution analysis clearly show the ef?cacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery.
152.
Makrigiorgos, M; Sridhar, S; D’Amico, A; Nguyen, P; Cormack, R
40 poster: Biological In-Situ Dose Painting for IGRT (BIS-IGRT) by Use of Drug-Loaded Implantable Fiducials and Spacers Journal Article
In: Radiotherapy and Oncology, vol. 94, pp. S18, 2010.
@article{makrigiorgos201040,
title = {40 poster: Biological In-Situ Dose Painting for IGRT (BIS-IGRT) by Use of Drug-Loaded Implantable Fiducials and Spacers},
author = {M Makrigiorgos and S Sridhar and A D’Amico and P Nguyen and R Cormack},
year = {2010},
date = {2010-01-01},
journal = {Radiotherapy and Oncology},
volume = {94},
pages = {S18},
publisher = {Elsevier},
abstract = {Conclusions: 18F-ML-10 holds promise for early detection of tumor response to radiation. Generating" Delta image" for mapping response is feasible, and these images may potentially be employed for planning a non-uniform dose administration and adjustment, conforming to differential radio-sensitivity of various regions within the tumor. Multi-center studies are ongoing to evaluate performance of 18F-ML-10 in predicting response of different tumors to radiation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Conclusions: 18F-ML-10 holds promise for early detection of tumor response to radiation. Generating" Delta image" for mapping response is feasible, and these images may potentially be employed for planning a non-uniform dose administration and adjustment, conforming to differential radio-sensitivity of various regions within the tumor. Multi-center studies are ongoing to evaluate performance of 18F-ML-10 in predicting response of different tumors to radiation.
153.
Gultepe, Evin; Nagesha, Dattatri; Casse, Bernard DF; Banyal, Ravinder; Fitchorov, Trifon; Karma, Alain; Amiji, Mansoor; Sridhar, Srinivas
Sustained Drug Release from Non-eroding Nanoporous Templates Journal Article
In: Small, vol. 6, no. 2, pp. 213–216, 2010.
@article{gultepe2010sustained,
title = {Sustained Drug Release from Non-eroding Nanoporous Templates},
author = {Evin Gultepe and Dattatri Nagesha and Bernard DF Casse and Ravinder Banyal and Trifon Fitchorov and Alain Karma and Mansoor Amiji and Srinivas Sridhar},
year = {2010},
date = {2010-01-01},
journal = {Small},
volume = {6},
number = {2},
pages = {213--216},
publisher = {WILEY-VCH Verlag Weinheim},
abstract = {We present the results for the release of a model drug, doxorubicin (Dox), fromdifferent non-eroding nanopor- ous coatings. Detailed studies of drug release from these platforms in the form of anodic aluminum oxide (AAO) and anodic titaniumoxide (ATO)were carried out. We show that nanoporous surfaces can achieve a sustained release rate over periods of several weeks, similar to polymeric platforms but without the risk of delamination or leaching since they are not degradable. We show that the kinetics of the sustained release from these nanoporous platforms is well described by an activated surface-density-dependent desorptionmodel,which appears to be universal for non-eroding platforms.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present the results for the release of a model drug, doxorubicin (Dox), fromdifferent non-eroding nanopor- ous coatings. Detailed studies of drug release from these platforms in the form of anodic aluminum oxide (AAO) and anodic titaniumoxide (ATO)were carried out. We show that nanoporous surfaces can achieve a sustained release rate over periods of several weeks, similar to polymeric platforms but without the risk of delamination or leaching since they are not degradable. We show that the kinetics of the sustained release from these nanoporous platforms is well described by an activated surface-density-dependent desorptionmodel,which appears to be universal for non-eroding platforms.
154.
Nagesha, DK; Tada, DB; Stambaugh, CKK; Gultepe, E; Jost, E; Levy, CO; Cormack, R; Makrigiorgos, GM; Sridhar, S
Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT) Journal Article
In: Physics in Medicine & Biology, vol. 55, no. 20, pp. 6039, 2010.
@article{nagesha2010radiosensitizer,
title = {Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)},
author = {DK Nagesha and DB Tada and CKK Stambaugh and E Gultepe and E Jost and CO Levy and R Cormack and GM Makrigiorgos and S Sridhar},
year = {2010},
date = {2010-01-01},
journal = {Physics in Medicine & Biology},
volume = {55},
number = {20},
pages = {6039},
publisher = {IOP Publishing},
abstract = {The therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs) . In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer Poly(methyl methacrylate) (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs) . In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer Poly(methyl methacrylate) (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.
155.
Tada, Dayane B; Singh, Surinder; Nagesha, Dattatri; Jost, Evan; Levy, Craig O; Gultepe, Evin; Cormack, Robert; Makrigiorgos, Mike G; Sridhar, Srinivas
Chitosan film containing poly (D, L-lactic-co-glycolic acid) nanoparticles: a platform for localized dual-drug release Journal Article
In: Pharmaceutical research, vol. 27, no. 8, pp. 1738–1745, 2010.
@article{tada2010chitosan,
title = {Chitosan film containing poly (D, L-lactic-co-glycolic acid) nanoparticles: a platform for localized dual-drug release},
author = {Dayane B Tada and Surinder Singh and Dattatri Nagesha and Evan Jost and Craig O Levy and Evin Gultepe and Robert Cormack and Mike G Makrigiorgos and Srinivas Sridhar},
year = {2010},
date = {2010-01-01},
journal = {Pharmaceutical research},
volume = {27},
number = {8},
pages = {1738--1745},
publisher = {Springer US},
abstract = {The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.
Purpose
To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release.
Methods
Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS).
Results
Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days.
Conclusions
The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.
Purpose
To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release.
Methods
Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS).
Results
Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days.
Conclusions
The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.
Purpose
To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release.
Methods
Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS).
Results
Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days.
Conclusions
The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.
156.
Cormack, Robert A; Sridhar, Srinivas; Suh, Warren W; D'Amico, Anthony V; Makrigiorgos, Mike G
Biological in situ dose painting for image-guided radiation therapy using drug-loaded implantable devices Journal Article
In: International Journal of Radiation Oncology* Biology* Physics, vol. 76, no. 2, pp. 615–623, 2010.
@article{cormack2010biological,
title = {Biological in situ dose painting for image-guided radiation therapy using drug-loaded implantable devices},
author = {Robert A Cormack and Srinivas Sridhar and Warren W Suh and Anthony V D'Amico and Mike G Makrigiorgos},
year = {2010},
date = {2010-01-01},
journal = {International Journal of Radiation Oncology* Biology* Physics},
volume = {76},
number = {2},
pages = {615--623},
publisher = {Elsevier},
abstract = {Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio.We model this new approach for two types of treatment. Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug prop- erties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for 4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of biologi- cally equivalent doses to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio.We model this new approach for two types of treatment. Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug prop- erties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for 4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of biologi- cally equivalent doses to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.
157.
Cormack, R; Nguyen, P; Amico, A D”; Sridhar, S; Makrigiorgos, M
MO-FF-A1-01: Optimal Schedule for Localized Radio-Sensitization of 125I Prostate Implants Journal Article
In: Medical Physics, vol. 37, no. 6Part26, pp. 3361–3361, 2010.
@article{cormack2010mo,
title = {MO-FF-A1-01: Optimal Schedule for Localized Radio-Sensitization of 125I Prostate Implants},
author = {R Cormack and P Nguyen and A D” Amico and S Sridhar and M Makrigiorgos},
year = {2010},
date = {2010-01-01},
journal = {Medical Physics},
volume = {37},
number = {6Part26},
pages = {3361--3361},
publisher = {American Association of Physicists in Medicine},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
158.
Nagesha, Dattatri K; Plouffe, Brian D; Phan, Minh; Lewis, Laura H; Sridhar, Srinivas; Murthy, Shashi K
Functionalization-induced improvement in magnetic properties of Fe 3 O 4 nanoparticles for biomedical applications Journal Article
In: Journal of Applied Physics, vol. 105, no. 7, pp. 07B317, 2009.
@article{nagesha2009functionalization,
title = {Functionalization-induced improvement in magnetic properties of Fe 3 O 4 nanoparticles for biomedical applications},
author = {Dattatri K Nagesha and Brian D Plouffe and Minh Phan and Laura H Lewis and Srinivas Sridhar and Shashi K Murthy},
year = {2009},
date = {2009-01-01},
journal = {Journal of Applied Physics},
volume = {105},
number = {7},
pages = {07B317},
publisher = {American Institute of Physics},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
159.
Sawant, Rishikesh M; Sawant, Rupa R; Gultepe, Evin; Nagesha, Dattatri; Papahadjopoulos-Sternberg, Brigitte; Sridhar, Srinivas; Torchilin, Vladimir P
Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles Journal Article
In: Journal of Nanoparticle Research, vol. 11, no. 7, pp. 1777, 2009.
@article{sawant2009nanosized,
title = {Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles},
author = {Rishikesh M Sawant and Rupa R Sawant and Evin Gultepe and Dattatri Nagesha and Brigitte Papahadjopoulos-Sternberg and Srinivas Sridhar and Vladimir P Torchilin},
year = {2009},
date = {2009-01-01},
journal = {Journal of Nanoparticle Research},
volume = {11},
number = {7},
pages = {1777},
publisher = {Springer Netherlands},
abstract = {Stable 30-50 nm polymeric polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to ‘plain’ SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG-PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stable 30-50 nm polymeric polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to ‘plain’ SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG-PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.
160.
Sridhar, S
Nanoplatforms for Nanomedicine Journal Article
In: 2009.
@article{sridhar2009nanoplatforms,
title = {Nanoplatforms for Nanomedicine},
author = {S Sridhar},
year = {2009},
date = {2009-01-01},
abstract = {Biocompatible nanomaterials are key components of novel approaches to addressing the major problems of modern medicine. A variety of nanoplatforms have emerged that have resulted in dramatic developments in imaging, early diagnosis and targeted delivery of therapeutics. Several varieties of nanoplatforms: metal, semiconducting polymeric and magnetic nanoparticles, liposomes, micelles, and nanoassemblies, have been developed that can enable efficacious delivery of drugs, DNA or energy to localized sites such as tumors, using targeting agents such as antibodies or guided navigation using magnetic fields. The optical properties of these nanoparticles offer an attractive alternative to the fluorophore-based staining and labeling of biological samples, and have potential use in a wide range of biological and physical applications. Magnetic nanoplatforms for theranostics combine multiple functionalities including imaging, magnetic guidance to the disease site, delivery of the drug payload through sustained as well as triggered drug release. Nanoporous coatings have been developed for implants, cardiovascular stents and fiducials used in image guided radio therapy. The non-erodable coatings show sustained release profiles that are comparable to those from erodible polymer platforms, but without the problems of delamination. A new doctoral program has also been established incorporating new courses and interdisciplinary research in nanomedicine.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Biocompatible nanomaterials are key components of novel approaches to addressing the major problems of modern medicine. A variety of nanoplatforms have emerged that have resulted in dramatic developments in imaging, early diagnosis and targeted delivery of therapeutics. Several varieties of nanoplatforms: metal, semiconducting polymeric and magnetic nanoparticles, liposomes, micelles, and nanoassemblies, have been developed that can enable efficacious delivery of drugs, DNA or energy to localized sites such as tumors, using targeting agents such as antibodies or guided navigation using magnetic fields. The optical properties of these nanoparticles offer an attractive alternative to the fluorophore-based staining and labeling of biological samples, and have potential use in a wide range of biological and physical applications. Magnetic nanoplatforms for theranostics combine multiple functionalities including imaging, magnetic guidance to the disease site, delivery of the drug payload through sustained as well as triggered drug release. Nanoporous coatings have been developed for implants, cardiovascular stents and fiducials used in image guided radio therapy. The non-erodable coatings show sustained release profiles that are comparable to those from erodible polymer platforms, but without the problems of delamination. A new doctoral program has also been established incorporating new courses and interdisciplinary research in nanomedicine.
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