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Development and Evaluation of Cucurbitacin B Microemulsion: the Effect of Oil Phase and Aqueous Phase on Drug Percutaneous Absorption Based on ATR-FTIR Spectroscopy and Molecular Modeling

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Abstract

The present study aimed to develop a cucurbitacin B microemulsion (CuB-ME) and investigate the mechanism of the enhanced drug skin absorption at the molecular level. Firstly, the pseudo-ternary phase diagrams were developed to evaluate the effect of composition on microemulsion properties systematically. The formulation composition types and ratios of oil phase, surfactant, co-surfactant, and aqueous phase were optimized by an in vitro skin permeation experiment, and the optimized formula was confirmed with the pharmacodynamics study. Furthermore, the molecular mechanism of enhanced skin permeation was investigated using ATR-FTIR and molecular modeling. As a result, the optimized CuB-ME formulation was composed of Azone:Tween 80:ethanol:water = 2.5:16.9:5.6:75.0 (w/w/w/w). The oil phase improved skin permeation by disordering the stratum corneum intercellular liquid, while the aqueous phase impacted the particle size of the microemulsion and permeability coefficient of the drug. Besides, the hydration state of skin lipid also enhanced drug permeation by the interaction of water and the polar head of ceramide. The in vitro skin permeation amount was 45.47 ± 10.39 μg/cm2, and no significant skin irritation was observed. The pharmacodynamics study demonstrated that CuB-ME had a significant therapeutic effect on the animal tumor model. In conclusion, the CuB-ME was developed successfully and the effect of the oil phase and aqueous phase on drug skin permeation was clarified at the molecular level.

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, No. 26 Huatuo Road, High & New Technology Development Zone, Benxi, 117004, Liaoning, China

    Qi Tian, Liang Fang, Chao Liu & Hui Xu

  2. Shanxi Institute for Food and Drug Control, Xi’an, 710065, Shanxi, China

    Jianbo Guo

  3. Department of General Surgery, General Hospital of Benxi Iron and Steel CO. LTD, Benxi, 117000, Liaoning, China

    Qi Zhang

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  1. Qi Tian
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Correspondence to Chao Liu or Hui Xu.

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The care and use of animals followed the NIH Guidelines for the Care and Use of Laboratory Animals, and all experiments complied with the criterion for animal use published by the Life Science Research Center of Shenyang Pharmaceutical University.

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Tian, Q., Guo, J., Zhang, Q. et al. Development and Evaluation of Cucurbitacin B Microemulsion: the Effect of Oil Phase and Aqueous Phase on Drug Percutaneous Absorption Based on ATR-FTIR Spectroscopy and Molecular Modeling. AAPS PharmSciTech 21, 258 (2020). https://doi.org/10.1208/s12249-020-01797-8

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