Platelet-derived extracellular vesicle drug delivery system loaded with kaempferol for treating corneal neovascularization

Abstract

Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be readily endocytosed due to their lipid bilayer membrane and nanoscale structure, enhancing the bioavailability and efficacy of their therapeutic effects. PEVs also contain various trophic factors that enhance their effectiveness as therapeutic agents. Given that nanomedicine provides benefits over traditional treatments for eye diseases by surpassing physical ocular barriers, PEVs combined with the anti-angiogenic agent, kaempferol (KM), were assessed for their capacity to inhibit abnormal blood vessel formation in the cornea. Characterization of the nanoparticles suggested the successful preparation of KM-loaded PEVs (PEV-KM) with a mean diameter of approximately 160 nm and an encapsulation efficiency of around 61 %. PEV-KM was effectively internalized into human vascular endothelial cells, resulting in inhibited function, as evidenced by lower wound closure rates, decreased tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed following the topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1 %) was found to decrease vessel formation in the injured cornea. However, the combination of PEV and KM (1 % PEV with KM 6 μg/mL) showed an even stronger effect in inhibiting CoNV and decreasing the expression of proangiogenic and inflammatory cytokines. Overall, our data suggests that the topical administration of PEVs, either alone or alongside KM (PEV-KM), is a promising therapy for the management of CoNV.