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评估固体脂质纳米粒在兔体内的体外抗真菌作用和眼部药代动力学。

Assessment to the Antifungal Effects in vitro and the Ocular Pharmacokinetics of Solid-Lipid Nanoparticle in Rabbits.

机构信息

Henan Eye Hospital, Henan Provincial People's Hospital & People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Nov 30;16:7847-7857. doi: 10.2147/IJN.S340068. eCollection 2021.

DOI:10.2147/IJN.S340068
PMID:34876813
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8643199/
Abstract

INTRODUCTION: Fungal keratitis (FK) remains a severe sight-threatening disease, and case management is difficult due to ocular intrinsic barriers and drug shortages. Econazole (ECZ), a broad-spectrum antifungal agent, is limited in ocular applications due to the poor water solubility and strong irritant property. METHODS: We successfully prepared solid-lipid nanoparticle-based ECZ eye drops (E-SLNs) by microemulsion method, and the physicochemical properties of E-SLNs were investigated. Corneal permeability, antifungal ability against spp., irritation and bioavailability compared to ECZ Suspension (E-Susp) were evaluated in vitro and in vivo. RESULTS: E-SLNs were a uniform and stable system which had an average particle size of 19 nm and a spherical morphology. E-SLNs also exhibited controlled release, enhanced antifungal activity without irritation. The pharmacokinetic analysis in vivo confirmed that E-SLNs showed an improved ocular bioavailability and the drug concentration in the cornea were above minimum inhibitory concentration (MIC) for 3 h after single administration. CONCLUSION: The E-SLNs colloid system is a promising therapeutic approach for fungal keratitis and could serve as a candidate strategy for other ocular diseases.

摘要

简介：真菌性角膜炎（FK）仍然是一种严重的致盲性疾病，由于眼内固有屏障和药物短缺，病例管理较为困难。由于水溶性差和刺激性强，广谱抗真菌药物酮康唑（ECZ）在眼部应用中受到限制。 方法：我们成功地通过微乳法制备了基于固体脂质纳米粒的酮康唑滴眼液（E-SLNs），并对 E-SLNs 的理化性质进行了研究。在体外和体内评估了 E-SLNs 与酮康唑混悬液（E-Susp）相比的角膜通透性、对 属真菌的抗真菌能力、刺激性和生物利用度。 结果：E-SLNs 是一种均匀稳定的系统，平均粒径为 19nm，呈球形形态。E-SLNs 还表现出控制释放、增强的抗真菌活性而无刺激性。体内药代动力学分析证实，E-SLNs 提高了眼部生物利用度，单次给药后 3 小时内，角膜中的药物浓度均高于最低抑菌浓度（MIC）。 结论：E-SLNs 胶体系统是治疗真菌性角膜炎的一种有前途的治疗方法，也可能成为其他眼部疾病的候选策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/968399eab5b6/IJN-16-7847-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/e0bb628297ae/IJN-16-7847-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/0bfe9558a457/IJN-16-7847-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a4a7791d94e6/IJN-16-7847-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a7c65178f4c6/IJN-16-7847-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a34577286699/IJN-16-7847-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/968399eab5b6/IJN-16-7847-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/e0bb628297ae/IJN-16-7847-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/0bfe9558a457/IJN-16-7847-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a4a7791d94e6/IJN-16-7847-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a7c65178f4c6/IJN-16-7847-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/a34577286699/IJN-16-7847-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016d/8643199/968399eab5b6/IJN-16-7847-g0006.jpg

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本文引用的文献

[1]
A dual-functional chitosan derivative platform for fungal keratitis.

Carbohydr Polym. 2022-1-1

[2]
Celastrol-based nanomedicine promotes corneal allograft survival.

J Nanobiotechnology. 2021-10-26

[3]
A retrospective study of the spectrum of fungal keratitis in southeastern China.

Ann Palliat Med. 2021-9

[4]
Update on the management of fungal keratitis.

Int Ophthalmol. 2021-9

[5]
Novel water soluble sterile natamycin formulation (Natasol) for fungal keratitis.

Eur J Pharm Sci. 2021-8-1

[6]
The global incidence and diagnosis of fungal keratitis.

Lancet Infect Dis. 2021-3

[7]
Incorporation of ion exchange functionalized-montmorillonite into solid lipid nanoparticles with low irritation enhances drug bioavailability for glaucoma treatment.

Drug Deliv. 2020-12

[8]
Effectively suppressed angiogenesis-mediated retinoblastoma growth using celastrol nanomicelles.

Drug Deliv. 2020-12

[9]
Integrated nanovesicular/self-nanoemulsifying system (INV/SNES) for enhanced dual ocular drug delivery: statistical optimization, in vitro and in vivo evaluation.

Drug Deliv Transl Res. 2020-6

[10]
Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization.

Int J Nanomedicine. 2019-4-8

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