Chitosan-coated liposomes for sustained levetiracetam delivery: In-silico and in-vitro evaluation

Levetiracetam (LEV), a second-generation antiepileptic drug with a short half-life (6-8 h), was encapsulated in chitosan-coated liposomes prepared by thin-film hydration (cholesterol: phosphatidylcholine, 1:1 ratio) to achieve sustained release and improved therapeutic efficacy. The optimized formulation exhibited high encapsulation efficiency (98 %) and controlled particle size (167 nm after chitosan coating), with spherical morphology and negative zeta potential (-35 mV) ensuring colloidal stability. In vitro release studies demonstrated pH-responsive kinetics, with sustained release in simulated intestinal fluid (SIF; 97 % over 72 h) versus gastric conditions (SGF; 76 % over 24 h), highlighting intestinal targeting potential. Chitosan coating enhanced mucoadhesion (2.8-fold increase in ex vivo studies) and improved biocompatibility (98-101 % cell viability in human fibroblasts). Complementary in silico analysis revealed hydrogen bonding between LEV and phospholipids (binding energy: -5.6 kcal/mol), explaining the high drug retention. The formulation maintained excellent physical and chemical stability for three months. These results position chitosan-coated liposomes as a promising strategy to extend LEV dosing intervals and enhance patient compliance, warranting further preclinical evaluation.