Tacrolimus-loaded chitosan-based nanoparticles as an efficient topical therapeutic for the effective treatment of atopic dermatitis symptoms

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...

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Published inInternational journal of biological macromolecules Vol. 273; no. Pt 1; p. 133005
Main Authors Lee, Jin Sil, Oh, Eunjeong, Oh, Hyeryeon, Kim, Sunghyun, Ok, Subin, Sa, Junseo, Lee, Jeung-Hoon, Shin, Yong Chul, Bae, Yong-Soo, Choi, Cheol Yong, Lee, Sangho, Kwon, Ho-Keun, Yang, Siyoung, Choi, Won Il
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.07.2024
Subjects
Atopic dermatitis
Chitosan
Nanoparticle
Tacrolimus
Topical delivery
Chitosan
Tacrolimus
Nanoparticle
Topical delivery
Atopic dermatitis
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Summary: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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ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2024.133005