The aim of this study was to formulate and characterize a nanocarrier for topical delivery of hydrophobic Calcipotriol drug for treatment of psoriasis disease. Microemulsion based chitosan hydrogel was selected as nanocarrier. Various microemulsion formulations were prepared and characterized to achieve a nanocarrier with minimum particle size, maximum zeta potential and high stability during the storage time. Characterization results confirmed the successful formation of a sample with the particle size of 26.09 ± 2.2 nm and high stability over six months. The hydrogel formulation of this sample had an appropriate viscosity with pseudo-plastic behavior as a non-Newtonian fluid. Then, in vitro drug release as well as the vitamin D3 serum level of nanocarriers at in vivo media were evaluated. Drug release profile from commercial psoriasis ointment showed a burst release behavior in which 95 % of the drug was released after 5 h, while the same amount of drug was released through microemulsion based hydrogel after 24 h in a controlled manner. In addition, drug penetration studies showed that a large amount of Calcipotriol from nanocarriers retained in the skin and its penetration through the skin was very low. Results of vitamin D3 analogue in rats showed a statistically reduction of vitamin D3 level in rats treated with hydrogel form in comparison to rats treated with commercial Calcipotriol ointment. Finally, it can be concluded that changing the usual form of Calcipotriol drug ointment into MBH has higher impact on psoriasis treatment

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