Chitosan-Based Intelligent Microneedles for Delivery of Amphotericin B Loaded Oleosomes: Antifungal Ocular Patch Targeting for Effective Against Fungal Keratitis Using Rabbit Model via TLR4/NLRP3 Pathway.
Sammar Fathy Elhabal, Saeed Abdul-Kareem Saeed Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed A El-Nabarawi, Sandra Hababeh, Kristina Zarif Attalla, Mai S Shoela, Jakline Nelson, Marwa Fady, Nahla A Elzohairy, Mariam E Amin, Heba Sabry Ahmed, Tassneim M Ewedah, Ibrahim Mousa, Ahmed Mohsen Elsaid Hamdan
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引用次数: 0
Abstract
Background: Fungal keratitis (FK), a major cause of blindness, remains challenging to treat due to poor drug penetration and antifungal resistance. Amphotericin-B (AmB), a water-insoluble and low-permeability, necessitates innovative delivery systems to improve its therapeutic efficacy.
Methods: AmB was encapsulated within oleosomes (Ole) prepared using the ethanol injection method, using phosphatidylcholine (Lipoid S100) and sodium oleate, resulting in nanosized spherical globules. The optimized Ole were characterized, then the selected Ole were incorporated into sodium polyacrylate/PEG/chitosan-based microneedles (AmB-Ole/MNs) to improve ocular delivery by creating transient microchannels on the eye surface.
Results: The optimized Ole showed a droplet size of (175 ± 0.78 nm), polydispersity index of (0.33 ± 0.04), zeta potential of (31 ± 0.43 mV), high entrapment efficiency (91±0.63%), and improved stability, bioavailability, and controlled drug release. The AmB-Ole/MNs system increases corneal penetration and contact time via transient microchannels in the eye surface, achieving sustained drug delivery over 72 hours with 70% ex vivo permeation over 80 hours compared to AmB. In vitro antifungal activity and histopathological examination showed that the AmB-Ole/MNs system has potent biofilm disruption (>90%) and 27 mm and 32 mm zones of inhibition against Candida albicans and Aspergillus niger, respectively. The Cytotoxicity test showed reduced AmB toxicity with biocompatibility and in vivo rabbit model, ocular tolerance by targeting TLR4/NLRP3 pathways and histopathological studies.
Conclusion: The AmB-Ole/MNs system as an innovative ocular delivery platform for fungal keratitis offers sustained drug release, enhanced permeation, potent antifungal activity, and reduced toxicity. AmB-Ole/MNs showed promise for ocular AmB delivery for FK.
背景：真菌性角膜炎（FK）是致盲的主要原因，由于药物渗透性差和抗真菌耐药性，治疗仍然具有挑战性。两性霉素- b （AmB）是一种不溶于水、低渗透的药物，需要创新的给药系统来提高其治疗效果。方法：采用乙醇注射法制备油小体（Ole），用磷脂酰胆碱（Lipoid S100）和油酸钠包封AmB，制备纳米级球形小球。对优化后的Ole进行了表征，然后将所选Ole掺入聚丙烯酸钠/聚乙二醇/壳聚糖基微针（AmB-Ole/MNs）中，通过在眼表面形成瞬时微通道来改善眼部给药。结果：优化后的Ole液滴大小为（175±0.78 nm），多分散指数为（0.33±0.04），zeta电位为（31±0.43 mV），包封效率为91±0.63%，具有良好的稳定性、生物利用度和控释效果。AmB- ole /MNs系统通过眼表面的瞬时微通道增加了角膜渗透和接触时间，与AmB相比，在80小时内实现了70%的体外渗透，持续72小时的药物递送。体外抗真菌活性和组织病理学检查表明，AmB-Ole/MNs系统对白色念珠菌和黑曲霉分别有27 mm和32 mm的生物膜破坏（> ~ 90%）和抑制区。细胞毒性试验表明，生物相容性和体内兔模型、靶向TLR4/NLRP3通路的眼耐受性和组织病理学研究均降低了AmB的毒性。结论：AmB-Ole/MNs系统作为一种创新的真菌性角膜炎眼部给药平台，具有药物持续释放、增强渗透、强抗真菌活性和降低毒性的特点。AmB- ole /MNs有望用于FK的眼部AmB输送。
期刊介绍：
The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area.
With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field.
Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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