Abstract
Tacrolimus (TAC), a calcineurin inhibitor used topically for T-cell-mediated skin diseases, faces challenges due to poor solubility and limited skin penetration. To address these limitations, a film-forming system (FFS) incorporating nanostructured lipid carriers (NLCs) was developed for enhanced topical delivery. TAC-loaded NLCs (TAC-NLC) were prepared via high-temperature and high-pressure homogenization and optimized using Box-Behnken design. The optimized TAC-NLC showed 102.7 nm particle size, 0.126 PDI, 80.5 % encapsulation efficiency, and 2.5 % drug loading. TAC-NLC@FFS demonstrated spherical morphology and improved skin adhesion. In vitro studies showed sustained drug release and reduced cytotoxicity. In a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model, TAC-NLC@FFS significantly reduced dermatitis scores compared to the negative control group (score at week 7: 3.5 ± 0.6 vs. 8.00 ± 1.2), with efficacy comparable to commercial ointments. Spleen weight, an indicator of systemic inflammation, was significantly reduced in all treatment groups, supporting anti-inflammatory activity. Additionally, serum IgE and IL-4 levels, key markers of allergic inflammation, were decreased in TAC-treated groups, with IL-4 reduction showing statistical significance. These findings suggest that TAC-NLC@FFS combines improved skin delivery and formulation stability with therapeutic efficacy, offering a promising strategy for the topical treatment of atopic dermatitis.
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Materials
TAC was purchased from Reyon Pharmaceuticals, Co., Ltd. (Seoul, Republic of Korea).
Capmul MCM NF was obtained from Abitec Corporation (Columbus, OH, USA).
Precirol ATO 5, Compritol 888 ATO, Gelucire 43/01, Gelucire 50/13, Gelucire 44/14, Labrafac CC, Lauroglycol 90, Capryol PGMC, Capryol 90, and Peceol were purchased from Gattefossé (Saint Priest, Cedex, France). Poloxamer 188, Poloxamer 407, polyoxyethylene 40 stearate (Myrj 52), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
Screening of lipids and surfactants
The solubility characteristics of tacrolimus (TAC) within the lipid matrix significantly influence the encapsulation efficiency (EE) and drug loading (DL) of nanostructured lipid carriers (NLCs) [29]. In this study, the solubility profile of TAC was evaluated in various solid lipids, liquid lipids, and surfactant solutions. Among the solid lipids tested, Compritol 888 ATO, Gelucire 43/01, Gelucire 44/14, Gelucire 50/13, glycerol monostearate (GMS), palmitic acid, and Precirol ATO 5, TAC
Jin Sil Kang, Young-Guk Na, Minki Jin, Gabsik Yang, Dong-Sung Lee, Jong-Suep Baek, Hong-Ki Lee, Cheong-Weon Cho, Film-forming system of optimized tacrolimus-loaded nanostructured lipid carriers for effective topical treatment of atopic dermatitis, European Journal of Pharmaceutics and Biopharmaceutics, Volume 216, 2025, 114871, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2025.114871.
