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- W4220747025 abstract "Tacrolimus ointment (Tac-Oint) treats mild, moderate, and severe psoriasiforms. However, thickened (inefficient penetration), dehydrated, and lipid deficient skin (low retention) limit its utility in severe psoriasiform. The microneedling process improves skin penetration, and nanostructured lipidic carrier (NLC) improves water and lipid level in the skin and its drug retention ability. Therefore, we developed Tac-NLC-Gel using Quality-by-Design-approach and compared its efficacy, with Tac-Oint-MN, against the Imiquimod-induced severe psoriasiform mice model. Spherical shape, negative charged NLC with diameter between 120 to 180 nm was transformed into Tac-NLC-Gel that possessed 5.3 ± 0.41 pH, 3200.89 ± 279.85 mPa viscosity, and excellent texture properties. Tac-NLC-Gel, due to hydrous polymer network and liquid lipid in NLC core, showed slow-release (52%), low permeation flux (3.12 ± 0.38 μgcm−2h−1), and high drug retention (67%) as compared to Tac-Oint in 24 h with 33% skin hydration in 8 days. However, microneedling resulted in low skin hydration, low retention, and 604 folds higher permeation due to increased porosity. Unlike Tac-Oint (followed paracellular diffusion), the distribution pattern of Tac-Oint-MN showed trans- and paracellular and Tac-NLC-Gel portrayed formation of carrier micro-conduits after trans-appendageal accumulation and transcellular diffusion. Tac-Oint-MN and Tac-NLC-Gel alleviated splenomegaly, Psoriasis area, severity index scores, and cytokine levels with improved macroscopic and behavioral conditions compared to those with the disease control group. Stability study supports the storage of the developed gel at 2–8 °C. In conclusion, both Tac-NLC-Gel and Tac-Oint-MN technologies have shown competitive relevance in treating severe psoriasiform; however, we recommend using Tac-NLC-Gel over Tac-Oint-MN in the hypothesized condition. The NLC-Gel benefits drug penetration and localization by improving skin hydration; however, Oint-MN provides faster skin penetration." @default.
- W4220747025 created "2022-04-03" @default.
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- W4220747025 date "2022-05-01" @default.
- W4220747025 modified "2023-09-29" @default.
- W4220747025 title "Relevance of NLC-gel and microneedling-assisted tacrolimus ointment against severe psoriasiform: In vitro dermal retention kinetics, in vivo activity and drug distribution" @default.
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- W4220747025 doi "https://doi.org/10.1016/j.jddst.2022.103272" @default.
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