Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles

Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering and transmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.The polymeric micelles prepared in this study could entrap up to 43.2±2.27？μg of ITRA per milliliter. All micelles showed mean diameter between 120–200？nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2？mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF) varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.Invasive pulmonary fungal infection is major infectious disease among immunosuppressed patients. Difficulty of early clinical diagnosis and poor response to the common antifungal treatment result in high mortality percent of patients. In the recent years many efforts done to found an alternative drug delivery strategies for antifungal agents [1,2]. Aerosolization of antifungal agents can be used for prophylaxis against pulmonary fungal infections. High drug concentration in the site of infection, non invasive route of administration and reduce systemic toxicities are some advantages of this route of administration [3].While amphotericin is an effective drug for treatment of fungal infec