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基于透明质酸修饰传递体的水凝胶促进吲哚美辛经皮传递

Hyaluronan-modified transfersomes based hydrogel for enhanced transdermal delivery of indomethacin.

机构信息

College of Food and Drug, Henan Functional Cosmetics Engineering & Technology Research Center, Luoyang Normal University, Luoyang, People's Republic of China.

出版信息

Drug Deliv. 2022 Dec;29(1):1232-1242. doi: 10.1080/10717544.2022.2053761.

DOI:10.1080/10717544.2022.2053761
PMID:35403516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9004534/
Abstract

Hyaluronic acid (HA), as a hygroscopic and biocompatible molecule, has displayed unique permeation enhancement in transdermal delivery systems. Hence, indomethacin (IND) was encapsulated in HA-modified transfersomes (IND-HTs) to enhance transdermal IND delivery to reduce adverse effects in this study. The physiochemical properties of IND-HTs were characterized. Results showed that the prepared IND-HTs were spherical and revealed good entrapment efficiency (87.88 ± 2.03%), with a nanometric particle size (221.8 ± 93.34 nm). Then, IND-HTs were further incorporated into a carbopol 940 hydrogel (IND-HTs/Gel) to prolong retention capacity on the skin. The release and skin permeation experiments of IND-HTs/Gel were carried out with the Franz diffusion cells. It was found that IND-HTs/Gel exhibited sustained drug release, as well as superior drug permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of HTs/Gel with a wider distribution and higher fluorescence intensity. The hematoxylin-eosin stained showed that HA improved the transdermal effect by changing the microstructure of skin layers and decreasing skin barrier function. In addition, IND-HTs/Gel showed significant analgesic activity in hot plate test and no potentially hazardous skin irritation. This study indicated that the developed IND-HTs/Gel could be a promising alternative to conventional oral delivery of IND by topical administration.

摘要

透明质酸（HA）作为一种吸湿性和生物相容性分子，在透皮给药系统中显示出独特的渗透增强作用。因此，本研究将吲哚美辛（IND）包封在 HA 修饰的传递体（IND-HTs）中，以增强透皮 IND 传递，减少不良反应。对 IND-HTs 的理化性质进行了表征。结果表明，所制备的 IND-HTs 呈球形，包封率良好（87.88±2.03%），粒径纳米级（221.8±93.34nm）。然后，将 IND-HTs 进一步掺入卡波姆 940 水凝胶（IND-HTs/Gel）中以延长在皮肤上的滞留能力。通过 Franz 扩散池进行了 IND-HTs/Gel 的释放和皮肤渗透实验。结果表明，IND-HTs/Gel 表现出持续的药物释放，以及更好的药物渗透和通过皮肤的通量。共聚焦激光扫描显微镜显示 HTs/Gel 的穿透性得到改善，分布更广泛，荧光强度更高。苏木精-伊红染色显示，HA 通过改变皮肤层的微观结构和降低皮肤屏障功能来提高透皮效果。此外，IND-HTs/Gel 在热板试验中表现出显著的镇痛活性，且无潜在危险的皮肤刺激性。本研究表明，所开发的 IND-HTs/Gel 可通过局部给药替代传统的 IND 口服给药，具有广阔的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/bae87a30552c/IDRD_A_2053761_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/999865b0e46d/IDRD_A_2053761_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/b7fb636f1add/IDRD_A_2053761_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/4f4cbdf2fcbd/IDRD_A_2053761_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/a2cb1aa5935f/IDRD_A_2053761_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/0fc7e97ea567/IDRD_A_2053761_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/0adc57bbfed5/IDRD_A_2053761_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/ef6ba26d1ef4/IDRD_A_2053761_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/bae87a30552c/IDRD_A_2053761_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/999865b0e46d/IDRD_A_2053761_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/b7fb636f1add/IDRD_A_2053761_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/4f4cbdf2fcbd/IDRD_A_2053761_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/a2cb1aa5935f/IDRD_A_2053761_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/0fc7e97ea567/IDRD_A_2053761_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/0adc57bbfed5/IDRD_A_2053761_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/ef6ba26d1ef4/IDRD_A_2053761_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096d/9004534/bae87a30552c/IDRD_A_2053761_F0008_C.jpg

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