Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus

Abstract

Low solubility of tacrolimus in carrier matrix and subsequent poor in vivo bioavailability was overcome by constructing modified nanolipid carrier (MNLC) as a novel approach. The aim of this study was to develop MNLC with enhanced drug solubility in carrier lipid matrix using lipophilic solubilizers for topical delivery. Comprehensive characterization of tacrolimus-loaded MNLC (T-MNLC) was carried out for particle size, morphology, and rheology. Lipid modification resulted in the formation of less perfect crystals offering space to accommodate the dissolved drug leading to high entrapment efficiency of 96.66%. Compatibility and mixing behavior of carrier constituents was evaluated using DSC, FT-IR, and (1)H NMR. T-MNLC displayed sufficient stability that could be attributed to possibility to reduce total lipid concentration in carrier. T-MNLC-enriched gels showed significantly higher in vitro drug release, skin permeation, and in vivo bioavailability with dermatopharmacokinetic approach in guinea pigs compared to commercial ointment, Protopic® as reference. Penetration-enhancing effect was confirmed using gamma scintigraphy in vivo in rats. Radioactivity remained localized in skin at the application site avoiding unnecessary biodisposition to other organs with prospective minimization of toxic effects. Skin irritation studies showed T-MNLC to be significantly less irritating than reference. Research work could be concluded as successful development of novel T-MNLC using lipophilic solubilizers to increase the encapsulation efficiency of colloidal lipid carriers with advantage of improved performance in terms of stability and skin localization.