To explore the performance of the cationic nanocarrier leciplex (LPX) in escalating the oral bioavailability of vancomycin hydrochloride (VAN) by promoting its intestinal permeability. With the aid of a D-optimal design, the effect of numerous factors, including lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type, on LPX characteristics, including entrapment efficacy (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential value (Z.P.), and steady-state flux (Jss) were assessed. The optimized formula was further evaluated in terms of morphology, ex vivo permeation, stability, cytotoxicity, and in vivo pharmacokinetic study. The optimized formula was spherical-shaped with 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/hr. Furthermore, the formula increased the intestinal permeability of VAN by 2.3-fold compared to the drug solution. Additionally, the formula was stable, revealed good mucoadhesive properties, and was well tolerated for oral administration. The in vivo pharmacokinetic study demonstrated that the VAN Cmax increased by 2.99-folds and AUC0-12 by 3.41-folds compared to the drug solution. These outcomes proved the potentiality of LPX in increasing the oral bioavailability of poorly absorbed drugs.

The two main issues impacting oral delivery are drug solubility and permeability. The FDA adopted the Biopharmaceutics Classification System (BCS) in 2000. The BCS categorizes drugs into four classes based on their solubility and permeability. For permeability improvement and bioavailability, many experimental systems are utilized. Numerous nanocarrier technologies have recently been utilized to increase drug permeability by employing nanocarrier systems such as lipid vesicles, polymeric and lipid nanoparticles, polymeric micelles, and submicron lipid emulsions. This review proposes innovative nano-delivery systems for permeability augmentation. It focuses on some illustrations of drugs with various nanosystems, how these systems were developed, and how they successfully boost intestinal drug permeability and bioavailability.