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Transdermal Enhancement Strategy of Lappaconitine: Alteration of Keratin Configuration by Counter-Ion

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Abstract

The objective of this study was to develop a lappaconitine (LA) transdermal patch with counter-ion to increase the transdermal permeability of the drug, and a theory of counter-ion altering the conformation of the skin keratin was put forward based on the in vitro skin permeation study and physicochemical properties of ion-pairs. Formulation factors including pressure sensitive adhesives (PSAs), drug-loading, counter-ions and molar ratios of counter-ion were screened by in vitro skin permeation study. The optimized formulation was composed of 7% LA, 1.5 mole cinnamic acid and AAOH (PSA containing hydroxyl group synthesized by our laboratory) as an adhesive matrix. The optimized patch was evaluated by the pharmacokinetic and analgesic pharmacodynamic studies. AUC0–t and pain inhibition ratio of the optimized patch were 2450.40 ± 848.52 h ng/mL and 81.18%, which showed good absorption into the skin and excellent analgesic effect. The mechanism of facilitated transdermal drug permeation by counter-ion was investigated by ATR-FTIR, thermal analysis, FTIR, XPS and molecular docking. The results indicated that after the formation of ion-pairs, the excess counter-ions would alter the conformation of the skin keratin, thus increasing the transdermal penetration of LA. In conclusion, the LA patch was successfully optimized, and the effect of counter-ions on the skin was clarified at the molecular level. These findings provided additional references for the application of counter-ion in the transdermal drug delivery system.

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Authors and Affiliations

  1. College of Pharmacy, Yanbian University, 977 Gongyuan Road, Yanji, Jilin, 133002, China

    Mingxin Li, Yu Cai & Liang Fang

  2. Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Chao Liu, Haoyuan Song & Liang Fang

Authors
  1. Mingxin Li
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  2. Chao Liu
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  3. Yu Cai
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  4. Haoyuan Song
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  5. Liang Fang
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Contributions

ML: methodology, investigation, formal analysis, data curation, writing—original draft. CL: supervision, writing—review and editing. YC: resources. HS: investigation, formal analysis, validation. LF: conceptualization, resources, project administration, funding acquisition.

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Correspondence to Liang Fang.

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Li, M., Liu, C., Cai, Y. et al. Transdermal Enhancement Strategy of Lappaconitine: Alteration of Keratin Configuration by Counter-Ion. AAPS PharmSciTech 23, 61 (2022). https://doi.org/10.1208/s12249-021-02190-9

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  • DOI: https://doi.org/10.1208/s12249-021-02190-9

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