Microneedle loaded with luteolin-colostrum-derived exosomes: a dropless approach for treatment of glaucoma

Abstract

Glaucoma, a leading cause of irreversible blindness, is marked by elevated intraocular pressure (IOP) and retinal ganglion cell death. Traditional IOP-lowering eye drops often fail to penetrate the ocular barrier, leading to suboptimal outcomes. Microneedles (MN), offer a promising minimally invasive and localized alternative. Our study aimed to formulate a naturally-derived nanodelivery system using Luteolin-loaded colostrum-derived exosomes (LUT-EX) and propolis in MN arrays for better ocular delivery. The isolated exosomes were uniform, averaging 50.83 nm in size, with a zeta potential of -21.89 mV. LUT-EX showed a 48-h sustained release and high safety with an IC50 of 356.3 µg/mL. Integrating LUT-EX and propolis into MN arrays achieved optimal dissolution in over one minute and maintained mechanical strength under 30 N compression. LUT-EX@MN increased LUT permeation through scleral tissues 2.6-fold compared to gel matrix formulations. It also showed a sustained IOP-lowering effect reaching the normal IOP level in the first 3h and sustained over 7 days. The integrated system significantly reversed glaucoma-induced changes in TNF-α, IL-8, MYOC, NRF2, TIMP1, and IL-1β levels, resembling those of the healthy group. It also boosted antioxidant activity, increasing glutathione peroxidase by 1.6-fold compared to glaucomatous rabbits. Thus, our study highlighted that the integration of LUT-EX into microneedle arrays presents a groundbreaking dropless approach for localized glaucoma treatment, offering enhanced therapeutic efficacy. This platform could revolutionize glaucoma management, paving the way for more effective and targeted ocular therapies.

Keywords: Bio-inspired; Extracellular vesicles; Herbal drug; Intraocular pressure; Microneedles; Propolis.