Development of dextran based nanomicelles in a dry powder formulation for pulmonary administration of niclosamide

Abstract

Inhalable dry powders containing dextran-behenic acid polymeric micelles (PM) were developed for the local delivery of niclosamide (NCL) to combat bacterial infections in the lungs of patients with cystic fibrosis. NCL loaded PM were prepared using dialysis method. Inhalable nanocomposites loaded with NCL were effectively prepared by co-spray drying the PM with inert carriers like mannitol and lactose. The physicochemical properties and in vitro deposition of the aerosolized nanocomposites were then evaluated. Additionally, the in vitro efficacy of the prepared formulations against staphylococcus aureus was assessed using the agar well diffusion method. The optimized formulation exhibited a particle size of 333.67 +/- 22.36 nm, a polydispersity index of 0.53 +/- 0.08, a zeta potential of -2.90 f 0.18 mV, an encapsulation efficiency of 52.07 f 3.88, a drug loading of 19.94 f 1.49, and a release efficiency of 54.04 f 3.11. Scanning electron microscopy also revealed that the nanomicelles were nearly spherical in shape. Both the NCL-loaded nanocomposite and PM demonstrated superior antibacterial efficacy at higher concentrations, as compared to free NCL and drug-free PM. It can be, therefore, concluded that dry powders embedding NCL-PM may serve as a viable alternative therapy for treating lung infections in patients with cystic fibrosis.