Effect of Chitosan on Mechanical Properties of Lipid Bilayers using Micropipette Aspiration

Abstract

Liposomes composed of phospholipids have been widely used as drug delivery vehicles for both hydrophilic and hydrophobic moieties due to several characteristics such as reduced side effects, cell-specific and controlled delivery of drugs for better therapeutics. But the use of liposomes is limited due to short circulation half-life and higher susceptibility to oxidation and hydrolysis leading to the leakage of drugs. To overcome these limitations liposomes are modified with both natural and synthetic polymers. The surface modification of liposomes with polymers influences the membrane mechanical properties and water permeability, which can directly affect the cellular uptake, drug release and encapsulation efficiency of the liposome. Among several polymers, chitosan - a biodegradable and biocompatible polymer has shown greater potential in improving the mucoadhesive property and stability of the liposomal formulation. The present study focuses on how the surface concentration of chitosan modulates the mechanical properties (bending and area compressibility moduli, water permeability and lysis tension) of SOPC vesicle using micropipette aspiration technique. Chitosan-vesicles were prepared using inverse phase emulsion method and the homogenous distribution of polymer on the bilayer surface was confirmed using FITC-tagged chitosan by confocal microscopy. The bending moduli of chitosan-vesicles were found to increase in a concentration-dependent manner compared to pure SOPC vesicles. However, area compressibility modulus does not show any significant difference. In addition, the effect of solution pH on chitosan vesicle showed a decrease in bending modulus at pH 4.5 as compared to neutral pH ∼7. The water permeability of chitosan coated vesicles decreased significantly as compared to SOPC vesicle. The lysis tension of chitosan-vesicles was not significantly different from that of SOPC vesicles with increasing chitosan concentration. These findings may contribute to the design of chitosan- liposomal drug delivery system.