Targeting Tacrolimus to Deeper Layers of Skin with Improved Safety for Treatment of Atopic Dermatitis

摘要

Atopic dermatitis (AD) is a chronically relapsing eczematous disorder of the skin which has a significant impact on both the pediatric and adult population worldwide. Tacrolimus have been the drug of choice for treatment of AD which inhibits early T-cell activation in gene transcription such as interleukins resulting in suppression of inflammation. However, despite being quite effective, the most common adverse events associated with tacrolimus use are low and variable bioavailability, burning sensation and pruritus at the site of application. These findings prompt for development of novel carrier which could effectively target the tacrolimus molecule to the site of action without producing undesirable side effects.Tacrolimus loaded lipid nanoparticles (T-LN) have been prepared by high pressure homogenization technique, optimized and characterized for particle size and its distribution, entrapment efficiency, DSC and rheology. FT-IR revealed no incompatibility and drug remained encapsulated in lipid phase. T-LN enriched gels revealed much higher in vitro drug release, skin penetration and enhanced skin accumulation compared to reference ointment, Protopic. T-LN also displayed significantly higher drug levels penetrating into deeper skin layers which are the target sites for tacrolimus action. In vivo skin retention and visualization of cutaneous uptake using Confocal laser scanning microscopy confirmed targeting potential and showed no irritation to rabbit skin with PI1 0.00. T-LN was more effective with significant skin targeting potential and enhanced safety, supporting superior performance with better patient compliance.