Abstract
Purpose :
Overcoming the burden of intravitreal injections represents an unmet need in retinal pharmacotherapy. NaMESys is a novel drug delivery systems composed of monophasic, optically isotropic, thermodynamically stable, clear and self-assembling dispersions formulated by oil, water, surfactants and cosurfactant. Aiming to delivery sorafenib to the posterior segment of the eye, NaMESys formulations were developed and characterized by stability and ocular biodistribution studies after single dose administration.
Methods :
NaMESys containing sorafenib were prepared by self-assembling method (phase titration method). The performance of preparations by means of stability and pharmacokinetic profile was evaluated. Long term (36 month 25±2°C/60±5%RH) and accelerated condition (6 month 40±2°C/75±5%RH) stability studies were conducted, chemical-physical parameters were evaluated at different time points. Bioavailability study in NZW rabbits (n=6 per time point) after single dose administration (50μL topical administration in the right eye) was conducted and sorafenib ocular distribution at t= 5, 15, 30, 60, 90, 120 min was quantified by LC-MS.
Results :
Long-term and accelerated stability data showed a stable profile of all chemical-physical parameters under study. The droplet size of the dispersed phase is equal or less than 30 nm with a very low polydispersity and the recovery percentage of sorafenib is within specification limits (95-105%) for all formulations. Biodistribution study showed that sorafenib was detected in cornea, vitreous, conjunctivae and sclera but not in the aqueous humor of the treated eye neither in tissues of the contralateral eye. In retina of treated eyes, sorafenib maximum content (170 ±80 ng/g) was observed 5 min after treatment and decreased rapidly 2h post dose and was not quantified in left untreated eye. Sorafenib was not detected in plasma between 5 min to 30 min post dose, maximum content was observed 2h after treatment.
Conclusions :
NaMESys was shown to allow topical delivery of poorly water-soluble drugs, such as sorafenib, increasing their penetration and bioavailability to the ocular posterior segment otherwise possible only by intravitreal injection. Data highlight a strong stability profile endowed with a low droplet size distribution guaranteeing a 36-month shelf life. NaMESys promises to be a tool to improve delivery strategies in retinal pharmacotherapy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.