Drug combination using an injectable nanomedicine hydrogel for glioblastoma treatment

Int J Pharm. 2019 Mar 25:559:220-227. doi: 10.1016/j.ijpharm.2019.01.042. Epub 2019 Jan 28.

Abstract

Lauroyl-gemcitabine lipid nanocapsules (GemC12-LNC) hydrogel, administered intratumorally or perisurgically in the tumor resection cavity, increases animal survival in several orthotopic GBM models. We hypothesized that GemC12-LNC can be used as nanodelivery platform for other drugs, to obtain a combined local therapeutic approach for GBM. Paclitaxel (PTX) was selected as a model molecule and PTX-GemC12-LNC formulation was evaluated in terms of physicochemical and mechanical properties. The PTX-GemC12-LNC hydrogel stability and drug release were evaluated over time showing no significant differences compared to GemC12-LNC. The drug combination was evaluated on several GBM cell lines showing increased cytotoxic activity compared to the original formulation and synergy between PTX and GemC12. Our results suggest that GemC12-LNC hydrogel can be used as nanodelivery platform for dual drug delivery to encapsulate active agents with different mechanisms of action to achieve a better antitumor efficacy against GBM or other solid tumors.

Keywords: Gemcitabine; Glioblastoma; Hydrogel; Local delivery; Nanomedicine; Paclitaxel.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / chemistry
  • Deoxycytidine / pharmacology
  • Drug Carriers / chemistry
  • Drug Combinations
  • Drug Liberation / drug effects
  • Gemcitabine
  • Glioblastoma / drug therapy*
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Injections / methods
  • Lipids / chemistry
  • Lipids / pharmacology
  • Mice
  • Nanocapsules / chemistry
  • Nanomedicine / methods
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Rats

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Drug Combinations
  • Hydrogels
  • Lipids
  • Nanocapsules
  • Deoxycytidine
  • Paclitaxel
  • Gemcitabine