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Chitosan-coated antifungal formulations for nebulisation

Albasarah, YY; Somavarapu, S; Stapleton, P; Taylor, KMG; (2010) Chitosan-coated antifungal formulations for nebulisation. Journal of Pharmacy and Pharmacology , 62 (7) pp. 821-828. 10.1211/jpp.62.07.0002.

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Objectives The aim of this study was to produce and characterise amphotericin B (AmB) containing chitosan-coated liposomes, and to determine their delivery from an air-jet nebuliser. Methods Soya phosphatidylcholine : AmB (100 : 1) multilamellar vesicles were generated by dispersing ethanol-based proliposomes with 0.9% sodium chloride or different concentrations of chitosan chloride. These liposomes were compared with vesicles produced by the film hydration method and micelles. AmB loading, particle size, zeta potential and antifungal activity were determined for formulations, which were delivered into a two-stage impinger using a jet nebuliser. Key findings AmB incorporation was highest for liposomes produced from proliposomes and was greatest (approximately 80% loading) in chitosan-coated formulations. Following nebulisation, approximately 60% of the AmB was deposited in the lower stage of the two-stage impinger for liposomal formulations, for which the mean liposome size was reduced. Although AmB loading in deoxycholate micellar formulations was high (99%), a smaller dose of AmB was delivered to the lower stage of the two-stage impinger compared to chitosan-coated liposomes generated from proliposomes. Chitosan-coated and uncoated liposomes loaded with AmB had antifungal activities against Candida albicans and C. tropicalis similar to AmB deoxycholate micelles, with a minimum inhibitory concentration of 0.5 μg/ml. Conclusions This study has demonstrated that chitosan-coated liposomes, prepared by an ethanol-based proliposome method, are a promising carrier system for the delivery of AmB using an air-jet nebuliser, having a high drug-loading that is likely to be effectively delivered to the peripheral airways for the treatment of pulmonary fungal infections. © 2010 Royal Pharmaceutical Society of Great Britain.

Type: Article
Title: Chitosan-coated antifungal formulations for nebulisation
DOI: 10.1211/jpp.62.07.0002
URI: http://discovery.ucl.ac.uk/id/eprint/1350496
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