Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections

Authors

Sammar Fathy Elhabal
Shrouk A Ghaffar
Raghda Hager
Nahla A Elzohairy
Mohamed Mansour Khalifa
Passant M Mohie
Rania A Gad
Nasreen N Omar
Mohammed H Elkomy
Mohammad Ahmad Khasawneh
Nashwa Abdelaal

Publication Date

12-1-2023

Journal

International Journal of Pharmaceutics: X

DOI

10.1016/j.ijpx.2023.100174

PMID

36908304

PMCID

PMC9992749

PubMedCentral® Posted Date

2-18-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Amphotericin-B, Lactoferrin, Candida albicans, Confocal laser scanning microscopy (CLSM), Draize test, Nanoparticles, Triblock polymers PLGA-PEG-PEI, Atomic force microscopy (AFM)

Abstract

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.