Preparation, Optimization and In Vitro Characterization of Fluticasoneloaded Mixed Micelles Based on Stearic Acid-g-chitosan as a Pulmonary Delivery System.

PURPOSE: The primary objective of this study was to optimize formulation variables and investigate the in vitro characteristics of fluticasone propionate (FP)-loaded mixed polymeric micelles, which were composed of depolymerized chitosan-stearic acid copolymer (DC-SA) in combination with either tocopheryl polyethylene glycol succinate or dipalmitoylphosphatidylcholine for pulmonary drug delivery.

METHODS: A D-optimal design was employed for the optimization procedure, considering lipid/ polymer ratio, polymer concentration, drug/ polymer ratio, and lipid type as independent variables. Dependent variables included particle size, polydispersion index, zeta potential, drug encapsulation efficiency, and loading efficiency of the polymeric micelles. Additionally, the nebulization efficacy and cell viability of the optimal FP-loaded DC-SA micellar formulations were evaluated.

RESULTS: The mixed polymeric micelles were successfully prepared with properties falling within the desired ranges, resulting in four optimized formulations. The release of FP from the optimal systems exhibited a sustained release profile over 72 hours, with 70% of the drug still retained within the core of the micelles. The nebulization efficiency of these optimal formulations reached up to 63%, and the fine particle fraction (FPF) ranged from 41% to 48%. Cellular viability assays demonstrated that FP-loaded DC-SA polymeric micelles exhibited lower cytotoxicity than the free drug but were slightly more cytotoxic than empty mixed micelles.

CONCLUSION: In conclusion, this study suggests that DC-SA/ lipid mixed micelles have the potential to serve as effective carriers for nebulizing poorly soluble FP.