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In Vitro and In Vivo Biological Assessment of Dual Drug-Loaded Coaxial Nanofibers for the Treatment of Corneal Abrasion

Tawfik, EA; Alshamsan, A; Abul Kalam, M; Raish, M; Alkholief, M; Stapleton, P; Harvey, K; ... Barker, SA; + view all (2021) In Vitro and In Vivo Biological Assessment of Dual Drug-Loaded Coaxial Nanofibers for the Treatment of Corneal Abrasion. International Journal of Pharmaceutics (120732) 10.1016/j.ijpharm.2021.120732. (In press).

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Abstract

The treatment of corneal abrasion currently involves the topical administration of antibiotics, with moxifloxacin HCl (0.5% w/v) eye drops being one of the most widely used treatments. Our previous work (Tawfik et al., 2020) involved the development of coaxial poly-lactic-co-glycolic acid (PLGA) and polyvinylpyrrolidone (PVP) nanofibers loaded with the antibiotic moxifloxacin HCl and the anti-scarring agent pirfenidone in the core (PVP) and shell (PLGA) respectively, with a view to the system comprising an ocular insert for the combination therapy of corneal abrasion. In this study, we examine the antimicrobial, anti-scarring and pharmacokinetic properties of the fibers alongside consideration of their toxicity and propensity for irritation. Minimum inhibitory concentration and zone of inhibition studies against S. aureus and P. aeruginosa were performed, while fibroblast cell viability and α-smooth muscle actin (α-SMA, a biomarker for scar formation) were measured using MTT and Western Blot assays, respectively. Pharmacokinetic studies and efficacy against infection were performed using a rabbit model, while ocular irritancy was assessed using the Draize test. The studies demonstrated that the antimicrobial activity of the moxifloxacin HCl was preserved following encapsulation into the nanofibers, while the downregulation of α-SMA was demonstrated using concentrations below the IC20 values (concentration required to decrease corneal fibroblast viability by no more than 20%). The pharmacokinetic study showed retention and sustained release of the moxifloxacin HCl over a 24-hour period, in contrast to equivalent eye drops which required four times daily dosing. Evidence of low level (according to the MMTS scale) irritation was detected for the nanofiber systems. Overall, the study has demonstrated that the dual drug-loaded nanofiber system shows potential for once daily dosing as an ocular insert for the treatment of corneal abrasion.

Type: Article
Title: In Vitro and In Vivo Biological Assessment of Dual Drug-Loaded Coaxial Nanofibers for the Treatment of Corneal Abrasion
DOI: 10.1016/j.ijpharm.2021.120732
Publisher version: https://doi.org/10.1016/j.ijpharm.2021.120732
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Corneal abrasion, corneal infection, electrospinning, dual drug-loaded coaxial nanofibers, moxifloxacin, pirfenidone
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10128641
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