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

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

Supplementary materials

This section provides the details regarding additional figures of results.

Figure S1 Dose–response curve for cytotoxicity with radiation and LG-PTX + radiation.

Abbreviation: LG-PTX, liposome-in-gel-paclitaxel.

Figure S2 (A) Tumor volume after fifth dose for mice in control, radiation and LG-PTX + radiation groups (*P<0.05, **P<0.05). (B) Tumor growth inhibition (TGI) for radiation and LG-PTX + radiation groups (*P<0.05).

Abbreviation: LG-PTX, liposome-in-gel-paclitaxel.

Acknowledgments

This work was funded by a seed grant from the Healthcare Consortium, Indian Institute of Technology Bombay, Mumbai, India.

Disclosure

The authors report no conflicts of interest in this work.