Cationic Leciplex Nanocarriers for Oral Delivery of Vancomycin Hydrochloride: Design Optimization and Pharmacokinetic Evaluation

The aim was to examine how the cationic nanocarrier leciplex (LPX) could boost the oral bioavailability of vancomycin hydrochloride (VAN) through enhancement of its permeation across the intestinal wall. A D-optimal design was employed to evaluate the impact of several variables—namely, lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type—on the attributes of LPX, such as entrapment efficiency (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential (Z.P.), and steady-state flux (Jss). The optimal formulation underwent additional characterization of morphological features, ex vivo permeation, storage stability, cytotoxicity, and in vivo pharmacokinetics. The optimal LPX displayed a spherical configuration, registering an E.E. of 85.2 ± 0.95%, a P.S. of 52.74 ± 0.91 nm, a P.I. of 0.21 ± 0.02, a Z.P. of + 60.8 ± 1.75 mV, and a Jss of 175.03 ± 1.68 µg/cm²/h. Compared with the plain drug solution, the formulation increased VAN’s intestinal permeation by 2.3-fold. The system also proved to be stable, exhibited strong mucoadhesive behavior, and was well accepted via the oral route. The in vivo pharmacokinetic assessment revealed that, compared with the drug solution, VAN’s Cmax increased 2.99-fold and its AUC0-12 increased 3.41-fold. Collectively, these results underscore the capability of LPX to elevate the oral bioavailability of drugs with inherently poor absorption.