Ex vivo diffusion and biodistribution studies of progesterone delivered to the eye using 3D-printed inserts

Three-dimensional (3D) printing has emerged as a powerful technology for the fabrication of personalized drug delivery systems. In this work, we developed and characterised 3D-printed ocular inserts for the sustained delivery of progesterone for retinal diseases related to oxidative stress. Semi-solid extrusion was used to obtain inserts from different blends, resulting in a PVA/PVP/methylcellulose/guar gum/propylene glycol formulation. It was evaluated in terms of physical properties, mechanical performance, moisture behaviour, morphology, ocular tolerance, in vitro release, ex vivo diffusion and ocular biodistribution. The printed inserts were compact, with a fine porous microstructure and showed good dimensional reproducibility, suitable tensile strength and flexibility for ocular handling. HET-CAM tests confirmed the absence of ocular irritation. Progesterone-loaded printed inserts provided sustained in vitro release over 48 h. Ex vivo studies on rabbit eyes showed corneal and scleral diffusion of progesterone, with higher accumulation in the sclera. Biodistribution experiments in porcine eyes using scleral inserts revealed detectable drug levels in all ocular tissues, with retinal concentrations of 9.88 ± 2.17 µg/g of tissue. Compared with moulded inserts, 3D-printed inserts exhibited reduced variability, indicating improved dosing precision and reproducibility. Overall, these results indicate that 3D-printed progesterone ocular inserts are non-irritant, effectively provide sustained delivery, and achieve retinal concentrations of the drug, supporting their potential as a customisable device for neuroprotective treatment of retinitis pigmentosa.