Highly Retina-Permeating and Long-Acting Resveratrol/Metformin Nanotherapeutics for Enhanced Treatment of Macular Degeneration

Abstract

The development of therapeutics for effective treatments of retinal diseases is significantly constrained by various biological barriers. We herein report a nanomedicine strategy to develop nanotherapeutics featured with not only high retinal permeability but also sustained bioactive delivery. Specifically, the nanotherapeutics are rationally designed via aminolysis of resveratrol-encapsulated polycaprolactone nanoparticles (R@PCL NPs), followed by the formation of amide linkages with carboxyl-terminated transacting activator of transcription cell penetrating peptide (T) and metformin (M). The R@PCL-T/M NP nanotherapeutics are demonstrated in vitro to possess persistent drug release profiles, good ocular biocompatibility, and potent bioactive activities for targeting prevailing risk factors associated with retinal diseases. In vivo studies indicate that single-dose intravitreal administration of the R@PCL-T/M NPs can effectively improve retinal permeability (∼15-fold increase), prevent loss of endogenous antioxidants, and suppress the growth of abnormal vessels in the retina with macular degeneration for 56 days. This high treatment efficacy can be ascribed to the enhanced retinal permeability of the nanotherapeutics in conjunction with the sustained pharmacological activity of the dual drugs (R and M) in the retinal pigment epithelial region. These findings show a great promise for the development of pharmacological nanoformulations capable of targeting the retina and thereby treating complex posterior segment diseases with improved efficacies.

Eudragit Films as Carriers of Lipoic Acid for Transcorneal Permeability

“…There are two main methods for ocular treatment, one is the application of active principles in the posterior eye segment [ 30 ], in which a more or less complicated intervention is required, generally through the application of an injection with all the disadvantages that it implies. Another method is topical application in the anterior segment of the eye.…”

Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration: Case Series

“…Despite this, new treatment modalities are being developed for the treatment of retinal pathologies. More recently, to overcome the drawbacks associated with injecting anti-VEGF, researchers have developed novel ocular pharmacological nanoformulations with multiple bioactive properties for enhanced treatment of age-related macular degeneration [ 28 ]. In conclusion, more studies with longer follow-ups are necessary for better defining physiopathology, epidemiology, and the actual role of the presence of BALAD in nAMD.…”

Observations for Sjögren’s Pigment Epithelial Reticular Dystrophy in a 16-Year-Old Boy—An Extremely Rare Retinal Case Report

“…In vitro, nanotherapeutics have been shown to possess persistent drug release profiles, good ocular biocompatibility, and potent bioactive activities for targeting prevailing risk factors associated with retinal diseases. Further advantages of these compounds lie in preventing the loss of antioxidants as well as inhibiting the growth of abnormal vessels [ 15 ]. This discovery may turn out to be revolutionary both in diseases for which treatment is currently known as well as in rare diseases for which therapies are still insufficient or lacking, such as Sjogren’s retinal dystrophy.…”