Preparation of chitosan-coated liposomes as a novel carrier system for the antiviral drug Triazavirin

• Published in: Pharmaceutical development and technology Vol. 23; no. 4; pp. 334 - 342
• Main Authors: Kozhikhova, Ksenia V., Ivantsova, Maria N., Tokareva, Maria I., Shulepov, Iliya D., Tretiyakov, Andrey V., Shaidarov, Lev V., Rusinov, Vladimir L., Mironov, Maxim A.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 21.04.2018
• Subjects: Antiviral Agents - administration & dosage; Antiviral Agents - chemistry; antiviral drugs; Azoles - administration & dosage; Azoles - chemistry; chitosan; Chitosan - analogs & derivatives; Coated Materials, Biocompatible - chemistry; coating; Drug Delivery Systems; Drug Liberation; Liposomes; Liposomes - chemistry; Particle Size; Surface Properties; Triazines - administration & dosage; Triazines - chemistry; Ugi reaction; antiviral drugs; chitosan; coating; Liposomes; Ugi reaction
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450.2016.1242624

Novel method for the coating of positively charged liposomes with modified chitosan was elaborated. Liposomes were prepared by stepwise extrusion through inorganic membranes (Anotop) of 0.2 and 0.1 μm pore sizes. Chitosan derivatives were synthesized via the Ugi multicomponent reaction. Several series of liposomal compositions were produced and their properties were compared in terms of particle size, polydispersity index (PDI), zeta potential and stability. The effect of various additives was investigated and the optimal composition of the lipid film was determined. The addition of the uncharged fatty esters allowed the diameter of the liposomes obtained by extrusion to be reduced to 145-150 nm with a PDI of 0.13-0.15. The prepared liposomes were loaded with the novel antiviral drug Triazavirin and used to determine the release profile. Triazavirin was included into liposome layer as a salt with biocompatible choline derivatives of limiting fatty acids. The appropriate lipid composition was used for the preparation of a larger quantity of liposomes coated by modified chitosan. It was shown that an appropriate combination of liposomes and polysaccharide layer potentially extended colloidal stability by up to 3 months and exhibited broad functional capabilities for surface modification.