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谷氨酸壳聚糖黏膜粘附微球作为杀微生物剂载体的潜力-抗疱疹活性和穿透人阴道上皮的行为。

Potential of mucoadhesive chitosan glutamate microparticles as microbicide carriers - antiherpes activity and penetration behavior across the human vaginal epithelium.

机构信息

Department of Pharmaceutical Technology, Medical University of Białystok, Bialystok, Poland.

Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.

出版信息

Drug Deliv. 2021 Dec;28(1):2278-2288. doi: 10.1080/10717544.2021.1992037.

DOI:10.1080/10717544.2021.1992037
PMID:34668816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8530489/
Abstract

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.

摘要

壳聚糖谷氨酸（gCS）喷雾干燥微球作为克服阴道杀微生物剂传递相关挑战的有前途的载体。本研究旨在阐明开发的 gCS 多单位载体与齐多夫定（ZVD）的穿透和粘膜粘附行为，ZVD 作为一种模型抗逆转录病毒药物，与人阴道上皮接触，然后检查在永生化人角质形成细胞 HaCaT 和人阴道上皮细胞 VK2-E6/E7 中的抗疱疹活性。ZVD 分散体和安慰剂微球作为对照。微球显示出可行的（可与商业阴道产品相媲美）粘膜粘附和粘膜保留特性，可用于分离的人阴道组织。穿透研究表明，gCS 增加了活性药物在阴道上皮中的积累，但出人意料的是，它并没有促进其穿透人体组织。最后，获得的抗病毒结果表明 gCS 作为一种辅助抗疱疹的潜力，其作用模式与阻断病毒附着有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/daa606a5094c/IDRD_A_1992037_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/69363236bcbe/IDRD_A_1992037_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/ec0df468c7af/IDRD_A_1992037_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/43d1718c5bd9/IDRD_A_1992037_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/d5c648688483/IDRD_A_1992037_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/a2e842900a27/IDRD_A_1992037_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/e8123c4fe4dd/IDRD_A_1992037_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/daa606a5094c/IDRD_A_1992037_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/69363236bcbe/IDRD_A_1992037_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/ec0df468c7af/IDRD_A_1992037_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/43d1718c5bd9/IDRD_A_1992037_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/d5c648688483/IDRD_A_1992037_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/a2e842900a27/IDRD_A_1992037_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/e8123c4fe4dd/IDRD_A_1992037_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f6/8530489/daa606a5094c/IDRD_A_1992037_F0007_B.jpg

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[3]
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[4]
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[5]
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本文引用的文献

[1]
Chitin and chitosan as tools to combat COVID-19: A triple approach.

Int J Biol Macromol. 2021-7-31

[2]
Tragacanth Gum/Chitosan Polyelectrolyte Complexes-Based Hydrogels Enriched with Xanthan Gum as Promising Materials for Buccal Application.

Materials (Basel). 2020-12-27

[3]
Evaluation of the Inhibitory Effects of and on the Adhesion of Seven Common Lower Genital Tract Infection-Causing Pathogens to Vaginal Epithelial Cells.

Front Med (Lausanne). 2020-6-19

[4]
Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance prediction.

Lancet Infect Dis. 2020-6-19

[5]
Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines.

Int J Nanomedicine. 2020-4-22

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Omeprazole Increases the Efficacy of Acyclovir Against Herpes Simplex Virus Type 1 and 2.

Front Microbiol. 2019-12-3

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Could spray-dried microbeads with chitosan glutamate be considered as promising vaginal microbicide carriers? The effect of process variables on the in vitro functional and physicochemical characteristics.

Int J Pharm. 2019-7-25

[8]
The improved antiviral activities of amino-modified chitosan derivatives on Newcastle virus.

Drug Chem Toxicol. 2021-7

[9]
Pharmaceutical Vehicles for Vaginal and Rectal Administration of Anti-HIV Microbicide Nanosystems.

Pharmaceutics. 2019-3-26

[10]
Prevalence of Herpes Simplex Virus Type 1 and Type 2 in Persons Aged 14-49: United States, 2015-2016.

NCHS Data Brief. 2018-2

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