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      저자 : Xiangyu You (검색결과 1 건)
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        Phenylboronic acid-functionalized gelatin–oleic acid nanoparticles for high loading and efficient transdermal delivery of Celastrol towards the treatment of psoriasis

        Jiangtao Su,Na Lin,Xiangyu You,Heshuang Dai,Meng Rao,Lu Ye,Fan Ye,Le Cai,Yuxin Chen,Gao Zhou,Xiaoxia Guo 한국고분자학회 2023 Macromolecular Research Vol.31 No.11

        Systemic toxicity, poor aqueous solubility, and poorly cell permeable ability hindered the clinical application of Celastrol. In this study, we aimed to design and synthesize an amphiphilic conjugate to encapsulate Celastrol into micelles to improve its water solubility, cellular membrane penetration, improving the clinic translation potential of Celastrol for the treatment of psoriasis. For this purpose, we first synthesized gelatin and oleic acid conjugate (GOC-1), and then covalently bonded 4-(3-boronophenylamino)-4-oxobutanoic acid (BPOA) with GOC-1 to form a stable GOC-2 conjugate which can self-assemble into micelles in aqueous solution. Celastrol (Cel) was physically encapsulated into the core of GOCs micelles. The dynamic stability, particle size, drug release, zeta potential, drug-loading efficiency, and surface morphology of Cel/loaded GOCs nano-micelles were determined. In addition, cell viability, cellular uptake of Cel/loaded GOC-2, and skin permeation and in vivo anti-psoriasis effect of Cel-loaded GOC-2 were investigated. Our results have shown that Cel/loaded GOC-1 and Cel/loaded GOC-2 have spherical shapes with diameters of around 200–300 nm. Compared to GOC-1, GOC-2 micelles showed higher drug-loading efficiency and excellent permeation ability in vitro. Moreover, Cel/GOC-2 micelles reduced erythema and white scales on the dorsal skin of psoriatic mice. In conclusion, BPOA attached GOC nanoparticles as a Celastrol carrier not only increase its water solubility but also improve drug-loading efficiency and cell permeation ability, exhibiting superior anti-psoriatic effect than the commercially available tacrolimus. Our work is expected to provide a facile approach to prepare nanocarrier for Celastrol to improve the clinic translation potential of Celastrol.

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