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

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 fra...

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Autores principales: GuhaSarkar, Shruti, Pathak, Kamal, Sudhalkar, Niyati, More, Prachi, Goda, Jayant Sastri, Gota, Vikram, Banerjee, Rinti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138055/
https://www.ncbi.nlm.nih.gov/pubmed/27942215
http://dx.doi.org/10.2147/IJN.S110525
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author GuhaSarkar, Shruti
Pathak, Kamal
Sudhalkar, Niyati
More, Prachi
Goda, Jayant Sastri
Gota, Vikram
Banerjee, Rinti
author_facet GuhaSarkar, Shruti
Pathak, Kamal
Sudhalkar, Niyati
More, Prachi
Goda, Jayant Sastri
Gota, Vikram
Banerjee, Rinti
author_sort GuhaSarkar, Shruti
collection PubMed
description 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 IC(50) 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.
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spelling pubmed-51380552016-12-09 Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot GuhaSarkar, Shruti Pathak, Kamal Sudhalkar, Niyati More, Prachi Goda, Jayant Sastri Gota, Vikram Banerjee, Rinti Int J Nanomedicine Original Research 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 IC(50) 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. Dove Medical Press 2016-12-01 /pmc/articles/PMC5138055/ /pubmed/27942215 http://dx.doi.org/10.2147/IJN.S110525 Text en © 2016 GuhaSarkar et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
GuhaSarkar, Shruti
Pathak, Kamal
Sudhalkar, Niyati
More, Prachi
Goda, Jayant Sastri
Gota, Vikram
Banerjee, Rinti
Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138055/
https://www.ncbi.nlm.nih.gov/pubmed/27942215
http://dx.doi.org/10.2147/IJN.S110525
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