Nanoparticles composed of polysaccharide chitosan and oligosaccharide alginate for strengthen transdermal delivery of tacrolimus in atopic dermatitis

The transdermal delivery system was developed to overcome the side effect derived from oral administration of tacrolimus in the treatment of atopic dermatitis (AD). The nanoparticles (NPs) composed of polysaccharide chitosan (C) and alginate oligosaccharide (AOS) were designed for the transdermal delivery of tacrolimus (TAC). The particle sizes of the drug-loaded TAC@A/C NPs and TAC@AOS/C NPs were 393.5 ± 9.0 nm and 315.1 ± 8.3 nm, respectively. The corresponding zeta potential were +26.1 ± 1.2 mV and +25.7 ± 1.2 mV, with encapsulation efficiencies of 75.1 ± 2.9 % and 79.2 ± 3.2 %, respectively. The cellular uptake of FITC-AOS/C NPs was higher than that of FITC-A/C NPs, resulting in a more pronounced reduction in cytokines (IL-6, IL-8, TNF-α, and IFN-γ) in inflammatory HaCaT cells. Combination of drug with nanocarriers shows a synergistic effect on anti-inflammatory activity, with CI values <1. TAC@NPs significantly reduced skin lesion score, ear thickness, IL-4 and IgE levels, and the number of mast cells in AD rats compared to untreated AD rats. The chitosan/alginate nanoparticles facilitate drug penetration through the skin barrier, thereby enhancing drug accumulation in the skin to exert therapeutic effects for AD. Tacrolimus-loaded alginate/chitosan (A/C) as well as alginate oligosaccharide/chitosan (AOS/C) nanoparticles transdermally delivered across the stratum corneum to downregulate cytokines (e.g., IL-6, IL-8, TNF-α, and IFN-γ) and reduce ROS in inflammatory human keratinocytes (HaCaT cells), and decrease IL-4/IgE levels and skin thickness in DNFB-stimulated atopic dermatitis Wistar rats.