Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro , ex-vivo and in-vivo studies.

Autor:	Elhabal SF; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt., Ghaffar SA; Tactical Medical Department, Caduceus Lane Healthcare, Alexandria 21532, Egypt., Hager R; Department of Medicinal Microbiology and Immunology, Faculty of Medicine King Salman International University, El-Tor, South Siniai, Egypt., Elzohairy NA; Air Force Specialized Hospital, Cairo 19448, Egypt.; Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt., Khalifa MM; Department of Human Physiology, Faculty of Medicine, Cairo University, Egypt.; Department of Human Physiology, College of Medicine, King Saud University, 62511, Saudi Arabia., Mohie PM; Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21532, Egypt., Gad RA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef (NUB), Beni-Suef, 62511, Egypt., Omar NN; Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt., Elkomy MH; Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia., Khasawneh MA; Department of Chemistry, College of Science U.A.E. University, Al-Ain, P.O. Box 17551, United Arab Emirates., Abdelaal N; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Jazyk:	angličtina
Zdroj:	International journal of pharmaceutics: X [Int J Pharm X] 2023 Feb 28; Vol. 5, pp. 100174. Date of Electronic Publication: 2023 Feb 28 (Print Publication: 2023).
DOI:	10.1016/j.ijpx.2023.100174
Abstrakt:	The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans , Fusarium, and Aspergillus flavus , and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co -loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo . The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections. Competing Interests: The authors wish to declare no interest is involved in this publication. (© 2023 The Authors.)
Databáze:	MEDLINE
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