Development of Novel Olmesartan Medoxomil Loaded Leciplex for Enhanced Oral Bioavailability: Formulation, Histopathological Analysis, and In Vivo Pharmacokinetic Studies

Abstract Olmesartan medoxomil (OLM), a widely prescribed antihypertensive agent, suffers from poor solubility and first pass metabolism, which lowers its bioavailability. This work aimed to develop novel cationic nanocarriers (LeciPlex) for OLM to enhance its dissolution and oral bioavailability. A central composite design (CCD) was employed to optimize OLM-loaded LeciPlex (OLM-LPX) formulations. The independent variables included lecithin amount, surfactant amount, and surfactant type. The influence of these factors on particle size (PS), entrapment efficiency (EE), surface charge (ZP), and cumulative in vitro drug release (CR) was thoroughly evaluated and examined. The optimized formulation underwent additional evaluation for ex vivo permeation, morphology, stability, in vivo histopathology, and pharmacokinetic studies. The optimized OLM-LPX exhibited desirable PS (149.23 ± 2.02 nm), ZP (+ 62.03 ± 2.45 mV), EE (82.25 ± 4.63%), and CR (88.87 ± 1.97% after 8 h), aligning well with the predicted CCD values. Ex vivo permeation of optimized OLM-LPX across rabbit intestine showed a cumulative OLM transport of 1973.1 ± 207.9 µg versus 909.9 ± 217.8 µg for OLM suspension, with a permeability coefficient 3.4-fold higher and a 2.17-fold increase in intestinal permeability. Transmission electron microscope images showed spherical-shaped and smooth particles. It also exhibited accepted stability over the predetermined storage period (90 days), showing neither sedimentation nor particle coalescence. The orally administered optimized OLM-LPX showed no evidence for inflammatory signs or mucosal damage within intestinal gut segments under histopathological examination. Pharmacokinetic evaluation in rats demonstrated that OLM-LPX achieved a C max of 3.48 ± 0.25 µg/mL versus 1.32 ± 0.21 µg/mL for suspension, extended t max (2 h vs. 1 h), and a markedly enhanced AUC ₀–∞ of 41.17 ± 3.41 µg·mL⁻¹·h compared to 11.48 ± 1.69 µg·mL⁻¹·h, corresponding to a relative bioavailability of 358.62%. Collectively, LPX may serve as an effective nanocarrier for effective oral administration of poorly soluble OLM, contributing to its enhanced bioavailability. Graphical Abstract