Chitosan or ε-polylysine-functionalized mucoadhesive liposomes for enhanced intracellular delivery of Isoniazid

Polymer decoration is a widely used method for surface modification of liposomes which is able to improve the stability of the vesicles, mechanical resistance to aerosolization, mucoadhesion and targeting capabilities. Chitosan, a biocompatible polysaccharide, is an excellent candidate for this purpose and it is largely employed for the development of liposomal formulation for pulmonary delivery. The cationic polymer ε-poly-l-lysine is widely used as a food preservative while its use as a stabilizer and mucoadhesive agent is less explored. Here we consider the use of Chitosan and ε-poly-l-lysine to improve the properties of anionic liposomes entrapping Isoniazid, an anti-tubercular drug, to obtain stable, mucoadhesive nanocarriers capable of delivering Isoniazid into cells, for potential nasal administration. By using the same procedure for both polymers, we obtained liposomes decorated with Chitosan and ε-poly-l-lysine with the optimal size range for potential nasal administration and pulmonary deposition, capable of ensuring the stability of the entrapped drug both after three months of storage and after nebulization. These polymer-decorated liposomes show safe and effective intracellular delivery of Isoniazid to BCG-lux-infected macrophages, reducing intracellular mycobacteria viability.