Preliminary Investigation on Simvastatin-Loaded Polymeric Micelles in View of the Treatment of the Back of the Eye.

Silvia Pescina,Cristina Padula,Adryana Clementino,Fabio Sonvico,Patrizia Santi,Sara Nicoli

doi:10.3390/pharmaceutics13060855

Abstract

There is increasing consensus in considering statins beneficial for age-related macular degeneration and in general, for immune and inflammatory mediated diseases affecting the posterior segment of the eye. However, all available data relate to oral administration, and safety and effectiveness of statins directly administered to the eye are not yet known, despite their ophthalmic administration could be beneficial. The aim was the development and the characterization of polymeric micelles based on TPGS or TPGS/poloxamer 407 to increase simvastatin solubility and stability and to enhance the delivery of the drug to the posterior segment of the eye via trans-scleral permeation. Simvastatin was chosen as a model statin and its active hydroxy acid metabolite was investigated as well. Results demonstrated that polymeric micelles increased simvastatin solubility at least 30-fold and particularly TPGS/poloxamer 407 mixed micelles, successfully stabilized simvastatin over time, preventing the hydrolysis when stored for 1 month at 4 °C. Furthermore, both TPGS (1.3 mPas) and mixed micelles (33.2 mPas) showed low viscosity, suitable for periocular administration. TPGS micelles resulted the best performing in delivery simvastatin either across conjunctiva or sclera in ex vivo porcine models. The data pave the way for a future viable ocular administration of statins.

Highlights

Age-related macular degeneration (AMD) represents one of the main conditions responsible for vision impairment in the adult population and the last World Health Organization forecast indicates 196 million people were affected by AMD in 2020 worldwide [1].In AMD, the progressive loss of photoreceptors located in the macula, a small area in central retina, is responsible for vision reduction and eventually blindness.The etiopathology of the disease is still unclear and two variants of AMD may occur: the most frequent is a non-neovascular condition, known as the dry form, while the neovascular type, is called wet form
We proposed the development of simvastatin-loaded polymeric micelles for targeting the back of the eye via the trans-scleral route, in view of the treatment of dry-AMD and, more in general, of inflammatory condition affecting the posterior segment
Due to different possible therapeutic effects statins might be introduced into the ocular framework, for the treatment of AMD

Summary

Introduction

Age-related macular degeneration (AMD) represents one of the main conditions responsible for vision impairment in the adult population and the last World Health Organization forecast indicates 196 million people were affected by AMD in 2020 worldwide [1].In AMD, the progressive loss of photoreceptors located in the macula, a small area in central retina, is responsible for vision reduction and eventually blindness.The etiopathology of the disease is still unclear and two variants of AMD may occur: the most frequent is a non-neovascular condition, known as the dry form, while the neovascular type, is called wet form. In AMD, the progressive loss of photoreceptors located in the macula, a small area in central retina, is responsible for vision reduction and eventually blindness. The dry form is characterized by the progressive development of drusen, i.e., extracellular debris deposits between Bruch’s layer and basal lamina of the retinal pigmented epithelium (RPE) and between RPE and retina (subretinal drusenoid deposits), responsible for a progressive and, later on, irreversible retinal damage [2]. The dry form may evolve into the neovascular type, which shows a quick retinal angiogenesis and can benefit from anti-VEGF agents, like bevacizumab, ranibizumab or pegaptanib. The presence of a lipidic matrix, and of cholesterol, explains the growing interest in lipid-lowering agents, like statins, as possible tool in reducing and evenly preventing the progression of degenerative mechanisms [6,7].

Methods

Results

Conclusion