Desenvolvimento e caracterização de lipossomas recobertos com quitosana para administração intranasal de montelucaste sódico

Abstract

Chitosan is a biodegradable, non-toxic polymer, with favorable biological properties, that presents great potential for being utilized in safe and efficient formulation for intranasal administration. Sodium montelukast (MTK) is a drug which utilization is well known as an auxiliary in the treatment of asthma. However, oral therapy with MTK presents disadvantages that can potentially be circumvented by its administration via the nasal route, but its utilization through this pathway had not yet been investigated. The objective of this work was to develop chitosan-coated liposomes containing MTK for administration trough the nasal route, and characterize the obtained liposomes in terms of encapsulation efficiency, stability and drug release. The in vivo plasma concentration profile was also studied, as the histopathological characteristics of the nasal cavity and trachea after nasal administration of the chitosan-coated liposomes in healthy rats, comparatively to the administration of the drug suspension. The liposomal vesicles obtained were about 150nm in size. The increase in the diameter after coating with chitosan showed that the surface of the liposomes was coated, and this result was confirmed by the change in the zeta potential from negative before coating to positive after coating. MTK encapsulation efficiency in the liposomes was superior to 98% due to the lipophilicity of the MTK molecule, and the encapsulation efficiency remained high during the stability study. The pH and zeta potential results during the stability study suggest that the phosphatidylcholine of the non-coated liposomes was degraded during the analyzed stability time, thus forming a carboxylic acid that was responsible for the pH augmentation and zeta potential reduction. Meanwhile the chitosan protected the coated liposomes from this degradation. The in vivo study revealed that the administration through the nasal route prolonged the MTK plasma concentration profile compared to the oral route, and that the release of MTK from the liposomes appeared to be more sustained then the drug in suspension. No alteration in the nasal or tracheal epithelium was observed during the morphological analysis. The sustained release of MTK caused by the nasal administration of the liposomes when compared to the free drug administration suggest that this carrier system and this route of administration present potential benefits for the asthma treatment with MTK.