title: 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 IC50of 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.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai.
authors.forename: Shruti
authors.initials: S
authors.lastname: GuhaSarkar
authors.affiliation: Department of Clinical Pharmacology.
authors.forename: Kamal
authors.initials: K
authors.lastname: Pathak
authors.affiliation: Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Navi Mumbai, Maharashtra, India.
authors.forename: Niyati
authors.initials: N
authors.lastname: Sudhalkar
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai.
authors.forename: Prachi
authors.initials: P
authors.lastname: More
authors.affiliation: Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Navi Mumbai, Maharashtra, India.
authors.forename: Jayant Sastri
authors.initials: JS
authors.lastname: Goda
authors.affiliation: Department of Clinical Pharmacology.
authors.forename: Vikram
authors.initials: V
authors.lastname: Gota
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai.
authors.forename: Rinti
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005782:Gels; D008081:Liposomes; D017239:Paclitaxel
keywords: concurrent radiotherapy; hydrogel; lipid nanocarrier; radiosensitizer; regional drug delivery