Rational design of a stable W/O lipid emulsion for enhanced oral delivery of vinblastine

Abstract

The transition from intravenous to oral administration of vinblastine sulfate (VLB) poses a major clinical challenge, primarily due to its extremely low and variable oral bioavailability. To address these inherent limitations, we rationally designed a stable water-in-oil (W/O) lipid emulsion (VLB-LE) through systematic interfacial engineering. A comprehensive screening and optimization process identified coconut oil, with its superior emulsification region in pseudo-ternary phase diagrams, as the optimal oil phase and cholesterol as the most effective permeation enhancer. The formulation was precisely optimized via Response Surface Methodology, yielding an emulsion with a small, uniform droplet size (0.61 ± 0.06 μm), a high negative zeta potential (-64.8 ± 10.8 mV), and an encapsulation efficiency of 96.42%. The W/O structure conferred exceptional stability, significantly protecting VLB against chemical and biorelevant degradation. Furthermore, it provided a sustained, pH-independent release profile and markedly enhanced intestinal permeation ex vivo. In vivo pharmacokinetic studies in rats demonstrated a remarkable 7.26-fold improvement in oral bioavailability compared to the control solution, achieving a relative bioavailability of 49.9%. The enhanced absorption directly translated to superior therapeutic outcomes, with VLB-LE exhibiting a 6.0-fold increase in cytotoxic potency and promoting apoptotic in HepG2 cells, correlated with effective cellular uptake. This study validates the rationally designed W/O emulsion as a robust and promising colloidal platform for the oral delivery of VLB, effectively integrating interfacial stabilization, enhanced permeation, and protective encapsulation to overcome the key biopharmaceutical challenges associated with oral chemotherapy.

Keywords: Anticancer activity; Interfacial engineering; Oral bioavailability; Vinblastine; W/O lipid emulsion.