Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot

Shruti GuhaSarkar,1 Kamal Pathak,2 Niyati Sudhalkar,3 Prachi More,1 Jayant Sastri Goda,3 Vikram Gota,2 Rinti Banerjee1 1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 2Department of Clinical Pharmacology, 3Department of Radiation Oncology, Advanced Cent...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	GuhaSarkar S, Pathak K, Sudhalkar N, More P, Goda JS, Gota V, Banerjee R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Liposome radiosensitizer chemoradiotherapy hydrogel regional drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/65024f020cde49ebb8565dc865337a0e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:65024f020cde49ebb8565dc865337a0e
record_format	dspace
spelling	oai:doaj.org-article:65024f020cde49ebb8565dc865337a0e2021-12-02T01:49:53ZSynergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot1178-2013https://doaj.org/article/65024f020cde49ebb8565dc865337a0e2016-12-01T00:00:00Zhttps://www.dovepress.com/synergistic--locoregional-chemoradiotherapy-using-a-composite-liposome-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shruti GuhaSarkar,1 Kamal Pathak,2 Niyati Sudhalkar,3 Prachi More,1 Jayant Sastri Goda,3 Vikram Gota,2 Rinti Banerjee1 1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 2Department of Clinical Pharmacology, 3Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Navi Mumbai, Maharashtra, India Abstract: The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC50 of 325±117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5×3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy. Keywords: radiosensitizer, hydrogel, regional drug delivery, concurrent radiotherapy, lipid nanocarrierGuhaSarkar SPathak KSudhalkar NMore PGoda JSGota VBanerjee RDove Medical PressarticleLiposomeradiosensitizerchemoradiotherapyhydrogelregional drug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6435-6448 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liposome radiosensitizer chemoradiotherapy hydrogel regional drug delivery Medicine (General) R5-920
spellingShingle	Liposome radiosensitizer chemoradiotherapy hydrogel regional drug delivery Medicine (General) R5-920 GuhaSarkar S Pathak K Sudhalkar N More P Goda JS Gota V Banerjee R Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
description	Shruti GuhaSarkar,1 Kamal Pathak,2 Niyati Sudhalkar,3 Prachi More,1 Jayant Sastri Goda,3 Vikram Gota,2 Rinti Banerjee1 1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 2Department of Clinical Pharmacology, 3Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Navi Mumbai, Maharashtra, India Abstract: The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC50 of 325±117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5×3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy. Keywords: radiosensitizer, hydrogel, regional drug delivery, concurrent radiotherapy, lipid nanocarrier
format	article
author	GuhaSarkar S Pathak K Sudhalkar N More P Goda JS Gota V Banerjee R
author_facet	GuhaSarkar S Pathak K Sudhalkar N More P Goda JS Gota V Banerjee R
author_sort	GuhaSarkar S
title	Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title_short	Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title_full	Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title_fullStr	Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title_full_unstemmed	Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title_sort	synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/65024f020cde49ebb8565dc865337a0e
work_keys_str_mv	AT guhasarkars synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT pathakk synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT sudhalkarn synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT morep synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT godajs synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT gotav synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot AT banerjeer synergisticlocoregionalchemoradiotherapyusingacompositeliposomeingelsystemasaninjectabledrugdepot
_version_	1718402842546405376

Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot

Ejemplares similares