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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
Publication Date
Jan 01, 2016
Identifiers
DOI: 10.2147/IJN.S110525
OAI: oai:dsapce.library.iitb.ac.in:123456789/21475
Source
DSpace at IIT Bombay
Keywords
License
Unknown
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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 (5x3 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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