Novel Gellan Gum-Based In Situ Nanovesicle Formulation of Docetaxel for Its Localized Delivery Using Depot Formation.

Abstract

In the present study, different in situ hydrogel formulations of docetaxel (DTX) based on biocompatible polymers such as Hyaluronic Acid (HA), poloxamer-407, chitosan and gellan gum were formulated to increase its therapeutic efficacy and reduce toxicity. DTX was loaded in nanovesicles (20 mg/mL equivalent to commercial strength) and further incorporated into the hydrogel bases to possess a dual rationale of protection against burst release and enhanced solubility of the drug. The optimized hydrogel formulation (NV-TPGS-3-GG-4) showed ideal rheological behavior and in situ characteristics at 37±0.5°C with sustained release of more than 144 h. The optimized formulation had instant in vitro gelation (2.8±0.3 min) with good injectability in comparison to the conventional commercial DTX injectable formulation having instant release (<2 h). Additionally, developed formulation exhibited an improved biodisponibility (25.1±0.2 h) in comparison to the commercially available formulation (1.7±0.1 h). The Solid Tumor Carcinoma model in Swiss albino mice revealed that the optimized formulation (based on gellan gum) showed better tumor reduction (85.7±1.2%) and lower toxicity as compared to the commercial formulation (77.3±1.3%). Pharmacokinetic and biodistribution studies demonstrated 3 to 4 times higher localization of drug in tumors. Our findings suggested that injectable gellan gum-based in situ hydrogel formulation can be an effective delivery system for DTX with enhanced solubility, reduced toxicity, and better targeting to the tumors for improved therapeutics.Graphical abstract.