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

Authors GuhaSarkar S, Pathak K, Sudhalkar N, More P, Goda JS, Gota V, Banerjee R

Received 13 April 2016

Accepted for publication 20 July 2016

Published 1 December 2016 Volume 2016:11 Pages 6435—6448

DOI https://doi.org/10.2147/IJN.S110525

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


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

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