Preparation of itraconazole-loaded liposomes coated by carboxymethyl chitosan and its pharmacokinetics and tissue distribution

Abstract

Liposomes are potential carriers for targeting and controlled drug delivery by the intravenous route. Carboxymethyl chitosan (CMC) is a ramification of chitosan with intrinsic water-solubility. The aim of this study is to prepare itraconazole-loaded liposomes coated by carboxymethyl chitosan (CMC-ITZ-Lips), to evaluate its physico-chemical characteristics and the tissue targeting after being injected intravenously (i.v.). This study uses a film dispersion method to prepare itraconazole-loaded liposomes (ITZ-Lips) prior to coating them with CMC. The concentrations of ITZ in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of ITZ-Sol, ITZ-Lips, and CMC-ITZ-Lips. CMC-ITZ-Lips had an average diameter of 349.3 ± 18 nm with a zeta potential of −35.71 ± 0.62 mV and the in vitro antifungal activity was not inhibited by the entrapment. The CMC-ITZ-Lips exhibited a longer elimination half life (t_1/2β) in vivo compared with ITZ-Sol and ITZ-Lips after i.v. injection to mice. The biodistribution in mice was also changed after ITZ was encapsulated in CMC coated liposomes. CMC-ITZ-Lips performed significant lung targeting efficiency with AUC, Te and Re of lung all showed obvious elevation. In this study itraconazole was successfully encapsulated into carboxymethyl chitosan-modified liposomes for application of injection.

Keywords::

• Liposomes
• itraconazole (ITZ)
• carboxymethyl chitosan (CMC)
• antifungal test
• pharmacokinetics
• biodistribution