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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Tacrolimus-loaded chitosan-based nanoparticles as an efficient topical therapeutic for the effective treatment of
Jin Sil Lee1, Eunjeong Oh2, Hyeryeon Oh1
1Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea; School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Cheomdan-gwagiro, 123, Buk-gu, Gwangju 61005, Republic of Korea.
Abstract:
Atopic dermatitis (AD) is a chronic cutaneous disease with a complex underlying mechanism, and it cannot be completely cured. Thus, most treatment strategies for AD aim at relieving the symptoms. Although corticosteroids are topically applied to alleviate AD, adverse side effects frequently lead to the withdrawal of AD therapy. Tacrolimus (TAC), a calcineurin inhibitor, has been used to treat AD, but its high molecular weight and insolubility in water hinder its skin permeability. Herein, we developed and optimized TAC-loaded chitosan-based nanoparticles (TAC@CNPs) to improve the skin permeability of TAC by breaking the tight junctions in the skin. The prepared nanoparticles were highly loadable and efficient and exhibited appropriate characteristics for percutaneous drug delivery. TAC@CNP was stable for 4 weeks under physiological conditions. CNP released TAC in a controlled manner, with enhanced skin penetration observed. In vitro experiments showed that CNP was non-toxic to keratinocyte (HaCaT) cells, and TAC@CNP dispersed in an aqueous solution was as anti-proliferative as TAC solubilized in a good organic solvent. Importantly, an in vivo AD mouse model revealed that topical TAC@CNP containing ~1/10 of the dose of TAC found in commercially used Protopic® Ointment exhibited similar anti-inflammatory activity to that of the commercial product. TAC@CNP represents a potential therapeutic strategy for the management of AD.
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