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用于两性霉素B递送的丝素蛋白纳米颗粒与热敏原位水凝胶的粘膜粘附混合系统：真菌性角膜炎治疗的潜在选择。

Mucoadhesive Hybrid System of Silk Fibroin Nanoparticles and Thermosensitive In Situ Hydrogel for Amphotericin B Delivery: A Potential Option for Fungal Keratitis Treatment.

作者信息

Chomchalao Pratthana, Saelim Nuttawut, Lamlertthon Supaporn, Sisopa Premnapa, Tiyaboonchai Waree

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.

College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.

出版信息

Polymers (Basel). 2024 Jan 3;16(1):148. doi: 10.3390/polym16010148.

DOI:10.3390/polym16010148
PMID:38201813
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10780372/
Abstract

The purpose of this work was to investigate the feasibility of a novel ophthalmic formulation of amphotericin B-encapsulated silk fibroin nanoparticles incorporated in situ hydrogel (AmB-FNPs ISG) for fungal keratitis (FK) treatment. AmB-FNPs ISG composites were successfully developed and have shown optimized physicochemical properties for ocular drug delivery. Antifungal effects against and in vitro ocular irritation using corneal epithelial cells were performed to evaluate the efficacy and safety of the composite formulations. The combined system of AmB-FNPs-ISG exhibited effective antifungal activity and showed significantly less toxicity to HCE cells than commercial AmB. In vitro and ex vivo mucoadhesive tests demonstrated that the combination of silk fibroin nanoparticles with in situ hydrogels could enhance the adhesion ability of the particles on the ocular surface for more than 6 h, which would increase the ocular retention time of AmB and reduce the frequency of administration during the treatment. In addition, AmB-FNP-PEG ISG showed good physical and chemical stability under storage condition for 90 days. These findings indicate that AmB-FNP-PEG ISG has a great potential and be used in mucoadhesive AmB eye drops for FK treatment.

摘要

本研究旨在探讨一种新型的两性霉素B包裹的丝素蛋白纳米粒原位水凝胶（AmB-FNPs ISG）眼科制剂用于治疗真菌性角膜炎（FK）的可行性。成功制备了AmB-FNPs ISG复合材料，并显示出其在眼部药物递送方面具有优化的物理化学性质。通过对角膜上皮细胞进行抗真菌作用及体外眼刺激试验，以评估复合制剂的疗效和安全性。AmB-FNPs-ISG联合系统表现出有效的抗真菌活性，且对人角膜上皮（HCE）细胞的毒性明显低于市售两性霉素B。体外和离体粘膜粘附试验表明，丝素蛋白纳米粒与原位水凝胶的组合可增强颗粒在眼表的粘附能力超过6小时，这将增加两性霉素B在眼部的滞留时间并减少治疗期间的给药频率。此外，AmB-FNP-PEG ISG在90天的储存条件下表现出良好的物理和化学稳定性。这些结果表明，AmB-FNP-PEG ISG具有巨大潜力，可用于制备用于治疗FK的粘膜粘附性两性霉素B滴眼液。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/d149011289a8/polymers-16-00148-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/72d77f6f2df9/polymers-16-00148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/8140db4f64f8/polymers-16-00148-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/fe501c8d8b4b/polymers-16-00148-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/c13051f9ccc4/polymers-16-00148-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/13e10a14c4c0/polymers-16-00148-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/30cb30adb4da/polymers-16-00148-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/3d943ec3617e/polymers-16-00148-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/d149011289a8/polymers-16-00148-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/72d77f6f2df9/polymers-16-00148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/8140db4f64f8/polymers-16-00148-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/fe501c8d8b4b/polymers-16-00148-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/c13051f9ccc4/polymers-16-00148-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/13e10a14c4c0/polymers-16-00148-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/30cb30adb4da/polymers-16-00148-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/3d943ec3617e/polymers-16-00148-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/10780372/d149011289a8/polymers-16-00148-g008.jpg

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引用本文的文献

[1]
Silk-based microparticles for the adsorption of methylene blue: formulations, characterization, adsorption study, molecular docking, and molecular dynamics simulation.

RSC Adv. 2025-4-30

[2]
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[3]
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[4]
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Theranostics. 2025-1-1

[5]
Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

PLoS One. 2024

本文引用的文献

[1]
Candida Biofilm Eye Infection: Main Aspects and Advance in Novel Agents as Potential Source of Treatment.

Antibiotics (Basel). 2023-8-2

[2]
Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: , and studies.

Int J Pharm X. 2023-2-28

[3]
Fungal Keratitis: Clinical Features, Risk Factors, Treatment, and Outcomes.

J Fungi (Basel). 2022-9-15

[4]
A Review of Commonly Used Methodologies for Assessing the Antibacterial Activity of Honey and Honey Products.

Antibiotics (Basel). 2022-7-20

[5]
Recent Perspectives in the Management of Fungal Keratitis.

J Fungi (Basel). 2021-10-26

[6]
Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections.

Drug Deliv Transl Res. 2022-4

[7]
Nanoparticle-Hydrogel Composite Drug Delivery System for Potential Ocular Applications.

Polymers (Basel). 2021-2-21

[8]
Strategies to prolong the residence time of drug delivery systems on ocular surface.

Adv Colloid Interface Sci. 2021-2

[9]
Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis.

Front Bioeng Biotechnol. 2020-12-21

[10]
Challenges to antimicrobial susceptibility testing of plant-derived polyphenolic compounds.

Arh Hig Rada Toksikol. 2020-12-31

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