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

Parsa Bayati; Masoud Ali Karami; Mahsa Toolabi; Zeinab Ahmadi; Safa Radmehr; Mehdi Safdarian

doi:10.1016/j.ijbiomac.2025.147682

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

Int J Biol Macromol. 2025 Sep 14;328(Pt 2):147682. doi: 10.1016/j.ijbiomac.2025.147682. Online ahead of print.

Authors

Parsa Bayati¹, Masoud Ali Karami², Mahsa Toolabi³, Zeinab Ahmadi¹, Safa Radmehr⁴, Mehdi Safdarian⁵

Affiliations

¹ Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
² Nanotechnology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: makarami@ajums.ac.ir.
³ Department of Pharmaceutical Chemistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Thalassemia & Hemoglobinopathy Research center, Health research institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁵ Nanotechnology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: msafdaryan@gmail.com.

PMID: 40957514
DOI: 10.1016/j.ijbiomac.2025.147682

Abstract

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.

Keywords: Ex vivo study; Mucoadhesive properties; Sustained release; Thin-film hydration.