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

Authors
 Jin Sil Lee  ;  Eunjeong Oh  ;  Hyeryeon Oh  ;  Sunghyun Kim  ;  Subin Ok  ;  Junseo Sa  ;  Jeung-Hoon Lee  ;  Yong Chul Shin  ;  Yong-Soo Bae  ;  Cheol Yong Choi  ;  Sangho Lee  ;  Ho-Keun Kwon  ;  Siyoung Yang  ;  Won Il Choi 
Citation
 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Vol.273(Pt 1) : 133005, 2024-07 
Journal Title
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
ISSN
 0141-8130 
Issue Date
2024-07
MeSH
Administration, Topical ; Animals ; Chitosan* / chemistry ; Dermatitis, Atopic* / drug therapy ; Dermatitis, Atopic* / pathology ; Disease Models, Animal ; Drug Carriers / chemistry ; Drug Liberation ; HaCaT Cells ; Humans ; Mice ; Nanoparticles* / chemistry ; Skin / drug effects ; Skin / metabolism ; Skin / pathology ; Skin Absorption / drug effects ; Tacrolimus* / administration & dosage ; Tacrolimus* / chemistry ; Tacrolimus* / pharmacokinetics ; Tacrolimus* / pharmacology ; Tacrolimus* / therapeutic use
Keywords
Atopic dermatitis ; Chitosan ; Nanoparticle ; Tacrolimus ; Topical delivery
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0141813024038108
DOI
10.1016/j.ijbiomac.2024.133005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Ho-Keun(권호근) ORCID logo https://orcid.org/0000-0003-3175-0376
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/200228
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