Nanomedicines for back of the eye drug delivery, gene delivery, and imaging

Abstract

Treatment and management of diseases of the posterior segment of the eye such as diabetic retinopathy, retinoblastoma, retinitis pigmentosa, and choroidal neovascularization is a challenging task due to the anatomy and physiology of ocular barriers. For instance, traditional routes of drug delivery for therapeutic treatment are hindered by poor intraocular penetration and/or rapid ocular elimination. One possible approach to improve ocular therapy is to employ nanotechnology. Nanomedicines, products of nanotechnology, having at least one dimension in the nanoscale include nanoparticles, micelles, nanotubes, and dendrimers, with and without targeting ligands, are making a significant impact in the fields of ocular drug delivery, gene delivery, and imaging, the focus of this review. Key applications of nanotechnology discussed in this review include a) bioadhesive nanomedicines; b) functionalized nanomedicines that enhance target recognition and/or cell entry; c) nanomedicines capable of controlled release of the payload; d) nanomedicines capable of enhancing gene transfection and duration of transfection; f) nanomedicines responsive to stimuli including light, heat, ultrasound, electrical signals, pH, and oxidative stress; g) diversely sized and colored nanoparticles for imaging, and h) nanowires for retinal prostheses. Additionally, nanofabricated delivery systems including implants, films, microparticles, and nanoparticles are described. Although the above nanomedicines may be administered by various routes including topical, intravitreal, intravenous, transscleral, suprachoroidal, and subretinal routes, each nanomedicine should be tailored for the disease, drug, and site of administration. In addition to the nature of materials used in nanomedicine design, depending on the site of nanomedicine administration, clearance and toxicity are expected to differ.

Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

“…To improve drug bioavailability, nanotechnology is being employed in several ophthalmic applications for retinal and choroidal vascular disorders. 11 For example, Ozurdex ® , a biodegradable dexamethasone implant composed of polylactic-co-glycolic acid, is being used for patients with diabetic macular edema or macular edema associated with uveitis. Iluvien ® , a nonerodible polyimide implant that releases fluocinolone acetonide, was also recently approved for the treatment of diabetic macular edema.…”

“…In addition, HSA increases drug solubility, protects drugs against oxidation, and enhances the drug half-life. 11,14 Indeed, an HSA-based formulation of the water-insoluble anticancer drug, paclitaxel, was approved by the US Food and Drug Administration and has been used for treating breast and pancreatic cancers. 15 In the present study, HSA was conjugated with PEG, a widely used polymer, for improving the solubility and biocompatibility of the drug delivery system.…”

Efficacy and safety of dendrimer nanoparticles with coexpression of tumor necrosis factor-α and herpes simplex virus thymidine kinase in gene radiotherapy of the human uveal melanoma OCM-1 cell line

“…[26][27][28] Nanomedicines having at least one dimension in the nanoscale include nanoparticles, micelles, nanotubes, and dendrimers, with and without targeting ligands, and are making a significant impact in the fields of ocular drug delivery and gene delivery. 29 Nanoparticles have better cellular uptake than larger particles. This uptake process is most likely by endocytosis, and has been utilized for gene delivery investigating the uptake of different-sized nanoparticles (20, 100, 500, 1,000, and 2,000 nm) into retinal pigment epithelial cells.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…Since drug loading in these systems is generally low, they might be limited to drugs that are effective at low therapeutic doses. Polymeric nanoparticles have been studied extensively for ocular drug delivery, and the FDA-approved polymer PLGA is one of the most investigated materials in the eye, in addition to polyvinyl alcohol, chitosan, and albumin (Kompella et al 2013).…”