Design and Development of Antibacterial/Anti-inflammatory Dual Drug-Loaded Nanofibrous Inserts for Ophthalmic Sustained Delivery of Gentamicin and Methylprednisolone: In Vitro Bioassay, Solvent, and Method Effects’ Evaluation

To overcome the challenges caused by the use of conventional ophthalmic dosageforms such as the fast elimination of the drug from the surface of the eye, in this study, dualdrug-loaded nanofibers were developed for sustained ophthalmic delivery of gentamicin (GNT)and methylprednisolone (MP). Moreover, the solvent effects, polymer mixtures, and method ofpreparation on the release profile of the prepared nanofibers, were evaluated.

The nanofibers were prepared using polycaprolactone (PCL), poly (lactic-co-glycolicacid) (PLGA), and polyvinyl alcohol (PVA) using electrospinning technique. Thereafter,seven optimized formulations were developed with different solvent mixtures and polymerconcentrations using various electrospinning methods. The physicochemical and mechanicalproperties of nanofibers were also evaluated, and the morphology of formulations wasobserved. The antibacterial efficacy was investigated and the in vitro release amounts of GNTand MP from nanofibers were estimated using the bioassay and ultraviolet-visible (UV-Vis)spectroscopy.

The developed G1, G4, G5, G6, and G7 had suitable mechanical properties andmorphologies with diameter ranging between 70-350 nm. The 1:1 v/v ratio of DMF/DCM inthe solvent mixture and using core-shell technique for the preparation, formed nanofibers withmore favorable release profiles. The optimized formulations indicated sustained-release mannerfor both drugs during 3-9 days and the antibacterial efficacy against Staphylococcus aureus.

Among all the prepared formulations, the nanofiber with core-shell structurepossessed the best sustained-release profiles of GNT and MP. The obtained results suggest thatthese nanofibers have a potential to be used as an insert in the eye for long-term release of thedrug.