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Unconventional Passive Enhancement of Transdermal Drug Delivery: toward a Mechanistic Understanding of Penetration Enhancers Releasing from Acrylic Pressure-Sensitive Adhesive of Patches

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Abstract

Purpose

Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-sensitive adhesive of patches and propose an unconventional enhancement of PEs efficacy.

Methods

PEs efficacy was evaluated both in drug permeation study and drug pharmacokinetic study. Confocal Raman spectroscopy was employed to observe PEs release behavior by mapping PEs dynamic distribution in skin. The mechanism of PEs release behavior was provided from molecular interaction and rheology using FT-IR, molecular docking, molecular dynamic simulation and rheometer, separately.

Results

The release behavior of PEs themselves greatly restricted their efficacy. By using PEG 400, an improvement of oleic acid (OA) release behavior was achieved, and the efficacy of OA was significantly enhanced with enhancing ratio (ER) from 2.69 to 4.10 and AUClast from 1574 ± 87 to 2664 ± 249 ng·h/mL, separately. The improvement of OA release behavior was primarily resulted from reduction of the interaction between OA and adhesive, which was caused by other small molecules with a strong ability in forming hydrogen bonds with adhesive. Also, the rigidity of adhesive was a factor in affecting PEs release behavior.

Conclusions

An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive.

Influence of PEs release behavior on drug permeation through skin and molecular mechanism

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Abbreviations

AUC :

The area under concentration-time curve

CED:

Cohesive energy density

D′ :

Diffusion coefficient

EO:

Ethyl oleate

ER :

Enhancing ratio

IPM:

Isopropyl myristate

LA:

Lauric acid

LOA:

Linoleic acid

MA:

Myristic acid

MD:

Molecular dynamic

ML:

Methyl laurate

MRT :

The mean residence time

MSD:

Mean squared displacement

OA:

Oleic acid

PEs:

Penetration enhancers

SC:

Stratum corneum

TEWL:

Transepidermal water loss

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Author information

Author notes

  1. Lijuan Zeng and Wenting Song contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China

    Lijuan Zeng, Wenting Song, Wanhua He, Jie Zhang, Yu Wang & Jianping Liu

  2. Department of Pharmaceutical Chemistry, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China

    Jinlei Bian

  3. Department of Forensic Medicine, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China

    Zhengsheng Mao

  4. Institute of advanced drug delivery technology, No. 10 Xinghuo Ave Jiangbei New Area, Nanjing, 210032, People’s Republic of China

    Danyi Quan

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  1. Lijuan Zeng
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Correspondence to Wenting Song, Danyi Quan or Jianping Liu.

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Zeng, L., Song, W., He, W. et al. Unconventional Passive Enhancement of Transdermal Drug Delivery: toward a Mechanistic Understanding of Penetration Enhancers Releasing from Acrylic Pressure-Sensitive Adhesive of Patches. Pharm Res 37, 169 (2020). https://doi.org/10.1007/s11095-020-02901-0

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