Novel gamma linoleic acid encased in situ lipogel for augmented anti-tumor efficacy against solid tumor: In vitro and in vivo evaluation

Abstract

Aim.
The present investigation intended to develop novel thermo-reversible gamma-linolenic acid-liposome-hydrogel (GLG) as an in-situ depot system for intratumoral chemotherapy.

Methods
Gamma-linolenic acid (GLA) entrapped liposome (GL) were prepared by ethanol injection method and homogenization. It was optimized using Box-Behnken design. To create the final GLG formulation, the GL was added to a 22% w/v poloxamer hydrogel. The gel degradation tests, in vitro release studies and characterization were carried out simultaneously. In-depth in vivo biodistribution, anti-tumor efficacy, safety testing and histological investigation was done on DMBA-induced-solid tumor-bearing rats.

Results
The optimized GL had a hydrodynamic particle size of 104.2 ± 2.15 nm, PDI of 0.158 ± 0.0019, % EE 85.17 ± 2.05%, and %DL 12.65 ± 1.33%. The TEM imaging revealed that GL had spherical shape, and was uniformly dispersed. The final GLG formulation was adequately stable after l GL in poloxamer hydrogel because no noticeable changes in particle size, PDI, % EE, and gelation time were noticed. In addition, GLG demonstrated sustained in vitro drug release over 120 h. In vivo, intra-tumoral injection of GLG formed a depot that exhibited prolonged tumor retention, drug release lasting for 120 h, and a special tumor inhibition rate compared to free GLA and GL.