Bacterial keratitis in animals presents challenges due to ocular structural barriers, hindering effective drug delivery. In this study, we used biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) to encapsulate the naturally occurring antimicrobial peptide OH-CATH30, an alternative to conventional antibiotics, for the treatment of bacterial keratitis in animals. Microspheres (MS) were prepared using a modified water-in-oil-in-water (W/O/W) double-emulsion method with optimized osmotic pressure. We conducted comprehensive evaluations, including in vitro characterization, encapsulation efficiency determination, in vitro release kinetics, and in vivo/vitro assessments of irritation and bacterial inhibition. The optimized method yielded microspheres with impressive encapsulation efficiency of 75.2 ± 3.62% and a loading capacity of 18.25 ± 5.73%, exhibiting a well-defined particle size distribution (200-1000 nm) and a ζ-potential of -17.3 ± 1.91 mV. The microspheres demonstrated initial burst release followed by sustained and controlled release in vitro. Both in vitro and in vivo tolerance tests confirmed the biocompatibility of the drug-loaded microspheres, as they did not elicit significant irritation in ocular tissues. Remarkable antibacterial effects were observed in both in vitro and in vivo experiments. Our developed PLGA microspheres show promise as an alternative therapeutic option for topical administration in managing keratitis, offering exceptional drug delivery capabilities, improved bioavailability, and potent antibacterial efficacy.
Keywords: OH-CATH30; PLGA; keratoconus; microspheres; tolerance; treatment.