Tawfik, Essam; (2019) Dual Drug-Loaded Electrospun Nanofibres for the Treatment of Corneal Diseases. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Corneal abrasion is a scratch on the surface of the eye, which can predispose a patient to corneal infection. Certain types of bacteria, such as Pseudomonas aeruginosa (P. aeruginosa) can lead to a more aggressive condition known as corneal ulcer. If this is left untreated, patients may suffer from vision loss. A potential approach to treat this clinical problem could be the administration of an anti-scarring agent and an antibiotic incorporated into one dosage form. This would accelerate the wound closure and treat any associated infection. In this study we have demonstrated the performance of electrospun fibres loaded with an anti-scarring agent pirfenidone and a broad spectrum antibiotic moxifloxacin in separate compartments of multi-axial fibres. An optimisation of the preparation of these fibres has been performed. Pirfenidone was embedded in a water insoluble polymer, PLGA, to form the outer layer of these fibres, while moxifloxacin was dispersed in a water soluble polymer, PVA or PVP, in the inner layer. This led to extension of the release of pirfenidone, while providing a suitably rapid release of moxifloxacin from the fibres. An in vitro release study was performed using a range of approaches to study the release of each drug. The efficacy of the antibiotic moxifloxacin was tested against a Gram positive bacteria, Staphylococcus aureus (S. aureus), and the Gram negative P. aeruginosa by the zone of inhibition microbiological study. However, the efficacy of pirfenidone released from the fibres has been verified by a Western blot technique. More specifically, this was demonstrated by reducing the expression of alpha smooth muscle actin (α-SMA) protein that is generally upregulated in response to an injury. Finally, an in vivo study has been done to compare the performance of the fibres to conventional eye drops against an infected eye. Overall, the findings suggest that the electrospun fibres are capable of extending the release of both drugs compared to the drugs in the solution form. Moreover, the antibiotic moxifloxacin has retained its effect against S. aureus, and P. aeruginosa. Finally, the drug-loaded fibres downregulated α-SMA, suggesting the accelerated healing of the injured cornea.

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