Ciprofloxacin nanocrystals liposomal powders for controlled drug release via inhalation

Abstract

This study was conducted to evaluate the feasibility of developing inhalable dry powders of liposomal encapsulated ciprofloxacin nanocrystals (LECN) for controlled drug release. Dry powders of LECN were produced by freeze-thaw followed by spray drying. The formulations contained sucrose as a lyoprotectant in different weight ratios (0.75:1, 1:1 and 2:1 sucrose to lipids), along with 2% magnesium stearate and 5% isoleucine as aerosolization enhancers. The powder physical properties (particle size, morphology, crystallinity, moisture content), in vitro aerosolization performance, drug encapsulation efficiency and in vitro drug release were investigated. The spray dried powders were comprised of spherical particles with a median diameter of ∼1 µm, partially crystalline, with a low water content (∼2% mass) and did not undergo recrystallization at high relative humidity. When dispersed by an Osmohaler® inhaler at 100 L/min, the powders showed a high aerosol performance with a fine particle fraction (% wt. <5 µm) of 66-70%. After reconstitution of the powders in saline, ciprofloxacin nanocrystals were confirmed by cryo-electron microscopy. The drug encapsulation efficiency of the reconstituted liposomes was 71-79% compared with the stock liquid formulation. Of the three formulations, the one containing a sucrose to lipids wt. ratio of 2:1 demonstrated a prolonged release of ciprofloxacin from the liposomes. In conclusion, ciprofloxacin nanocrystal liposomal powders were prepared that were suitable for inhalation aerosol delivery and controlled drug release.

Keywords: Ciprofloxacin; Controlled drug release; Liposomes; Nanocrystals; Spray drying.