International Journal of Nanomedicine (Dec 2016)

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

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

Journal volume & issue
Vol. Volume 11
pp. 6435 – 6448

Abstract

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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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