Design of glycol chitosan-decorated liposomes for the intranasal delivery of hydrophilic substances: physicochemical and in vitro/in vivo biological assessment

Abstract

The surface of phosphatidylcholine-based liposomes was decorated with mucoadhesive polymer glycol chitosan (GC) to enhance the penetration of hydrophilic substance encapsulated therein from the nose to the brain. The composition of coated liposomes (chitosomes) was optimized by evaluating physicochemical characteristics, including hydrodynamic diameter, zeta potential, and polydispersity index. Particle stability over time was assessed, and both in vitro and in vivo biological tests were conducted using the leading system. Deposition of the polymer onto the liposome surface increased both the particle size (from 100 nm to 150 nm) and the zeta potential (from −75 mV to +42 mV) at the optimal GC/lipid wt. ratio of 1/10. Chitosome stability depends on storage temperature, and is maintained for up to 3 months at optimal component ratio. Hemagglutination and hemolytic activity were only observed at high concentrations of components beyond optimal compositions. The encapsulation efficiency of Rhodamine B (RhB) in optimized chitosomes was approximately 80 %, which was 20–25 % higher than that observed in liposomes. The chitosomes showed enhanced cellular internalization compared to conventional liposomes. Spectrophotometric analysis revealed that nearly complete release of RhB occurred from liposomes within 7 h, while only 70 % of RhB was released from chitosomes during the same period. Fluorescence microscopy tests demonstrated that intranasal administration of chitosomes led to their effective penetration into the rat brain in vivo.