Ethosomal Nanoformulations for Combinational Photothermal Therapy of Fungal Keratitis

Abstract

Fungal keratitis/mycotic keratitis or keratomycosis, is characterized by the inflammation of underlying stroma of corneal epithelium due to fungal infection. Multi‐drug resistance and subsequent recurrence of infection limits the clinical outcomes of anti‐fungal agents such as Amphotericin B and Natamycin; and therefore, demands research on newer anti‐microbial strategies. In this study, the authors have synthesized and characterized ethosomes (IAEs) encapsulating a NIR dye, Indocyanine green (ICG), and an anti‐fungal drug, Amphotericin B, for a combinational photothermal therapy of fungal keratitis. The in vitro anti‐fungal efficacy of the IAEs is validated against Candida albicans by colony formation assay, calcofluor staining, and SEM analysis. The results indicate that the IAEs, upon NIR irradiation, displays a synergistic anti‐fungal efficacy. The IAEs are highly biocompatible when tested using a human corneal epithelial (HCE) cell line model (in vitro) and a Draize eye test model in rabbits (in vivo). Further, it is observed that the IAEs,upon NIR laser exposure significantly eliminate the fungal infection in rat model of occular fungal keratitis. The research indicates that the IAEs nano‐formulation exhibits a synergistic and sustained anti‐fungal effect paving its way for further translation from bench to bedside for the efficient management of fungal keratitis.

Accelerating Diabetic Wound Healing by Modulating the Inflammatory Environment Using Quercetin–Rosemary Oil Lipid Nanoemulsions with Artificial Intelligence‐Based Wound Closure Analysis

“…The same procedure was used for untreated groups. [ 74,75 ] After the incubation, the variation in the number of spots was assessed. Statistical analysis was conducted using a one‐way analysis of variance (ANOVA) to determine the significance of the results.…”

Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery

“…Due to their smaller size and elastic shape compared to typical liposomes, they enable local transport of both hydrophilic and hydrophobic active molecules and can enhance drug penetration or localization [ 78 , 79 ]. The comparative study revealed that ethosomal formulations exhibited more drug penetration into the cornea than liposomal formulations [ 80 ].…”

“…In research, Sushma et al (2023) designed ethosomes (IAEs) for a combination photothermal therapy of fungal keratitis that contains the near-infrared (NIR) dye, Indocyanine green (ICG), and the anti-fungal drug Amphotericin B [ 80 ]. Ethosomes were prepared by the TFH method.…”

“…In studies conducted on Ethosomes/Transethosomes up to the present, it has been determined that the TFH method is the production method utilized [ 77 , 78 , 79 , 80 , 81 ]. Interestingly, the ophthalmic Ethosomal/Transethosomal carrier systems prepared using the TFH method have demonstrated entrapment efficiencies ranging between 80% and 90%, a notable contrast to ocular liposomal and niosomal systems [ 77 , 81 ].…”

Ethosomes as Promising Transdermal Delivery Systems of Natural‐Derived Active Compounds

“…Considering biocompatibility and immunogenicity, several studies suggest a generally good biocompatibility profile of ethosomes; however, in some cases, they have been found to cause immune stimulation. A study devoted to the topical application of ethosomes loaded with an antifungal drug (amphotericin B) and a photoresponsive dye (indocyanine green) for the treatment of fungal infection in the cornea [ 60 ] showed high biocompatibility following tests on human corneal epithelial (HCE) cells and basing on a Draize eye test model in rabbits. In another study, ethosomes were evaluated on dendritic cells (DCs) in order to analyze their immune stimulatory effect.…”