Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery

Abstract

Yin-Ku Lin1,2, Zih-Rou Huang3, Rou-Zi Zhuo3, Jia-You Fang3,41Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kweishan, Taoyuan, Taiwan; 2Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; 3Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 4Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaAbstract: The combination of calcipotriol with methotrexate can strengthen the topical therapy for psoriasis. The aim of the present study was to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with lipophilic calcipotriol and hydrophilic methotrexate as topical therapy. NLCs composed of Precirol ATO 5 with various amounts of squalene as the liquid lipid were prepared. The particle size, surface charge, molecular environment, drug permeation, and skin irritation of the carriers were assessed. Hyperproliferative skin was also used as a permeation barrier in this study. It was found that variations in the Precirol®/squalene ratio had profound effects on the physicochemical characteristics of the NLCs. The range of particle size of the NLC preparations was 270 to 320 nm, with vehicles containing a higher Precirol amount exhibiting a larger diameter. NLCs with a higher Precirol/squalene ratio also showed greater polarity in their molecular environment. Calcipotriol-loaded NLC systems provided drug fluxes of 0.62 to 1.08 μg/cm2/h, which were slightly higher or comparable to the 30% ethanol vehicle (control, 0.72 μg/cm2/h). The methotrexate amount permeating the skin was 2.4 to 4.4-times greater using NLCs compared to that with the control. Dual drugloaded NLCs exhibited reduced skin permeation of calcipotriol but not methotrexate. The in vivo topical delivery examined by confocal laser scanning microscopy (CLSM) showed a good correlation with the in vitro results. These two drugs with extremely different polarities can successfully be combined in NLCs. Results suggest that NLCs may have the potential to serve as delivery carriers for antipsoriatic drugs because of enhanced drug permeation and limited skin irritation.Keywords: psoriasis, calcipotriol, methotrexate, nanostructured lipid carriers, topical delivery