From Parenteral to Oral Delivery: Facile Formulation of Oral Gemcitabine Nanospanlastics for Enhanced Bioavailability and Anticancer Activity in Murine Breast Cancer Model

Abstract

Gemcitabine hydrochloride (GEM) is a commonly used antineoplastic that is delivered only by intravenous infusion due to its limited oral bioavailability of 10%. The study aims to design and optimize novel Spanlastics (GEM-SLs) to improve the GEM's oral anticancer delivery. The GEM-SLs were facilely formulated, optimized, and investigated for enhanced intestinal permeability and oral bioavailability using an in situ perfusion procedure and pharmacokinetic study, respectively. The antitumor activity and biosafety were studied using normal and breast cancer cell lines in vitro, and the Solid Ehrlich Carcinoma (SEC) model in vivo. The size of GEM-SLs ranged from 72.1 to 171.4 nm, and the entrapment effectiveness ranged from 25% to 69.6%. The optimum GEM-SLs exhibited a 3 and 1.4-fold enhancement in the fraction of GEM absorbed from duodenal and jejuno-ileal regions, respectively. GEM-SLs showed an 8.3-fold enhancement in the oral bioavailability compared to oral free GEM. The superior cytotoxicity of GEM-SLs was accompanied by greater in vitro biosafety. The in vivo model showed significant reductions in tumor weight, volume, and histopathological parameters, supplemented with higher biosafety in comparison to the oral free drug. This research highlighted the ability of SLs to boost the oral bioavailability of GEM relative to the oral free drug and hence its oral therapeutic efficacy.