Recent advances in slow and sustained drug release for retina drug delivery

Abstract

Highlights: • Drug delivery remains a major challenge in the treatment of retinal diseases • Degradable and non-degradable implants for the sustained and local release of glucocorticoids have been approved • Bolus of proteins neutralizing VEGF family members allow the maintenance of clinical benefit for 1 to 3 months • New reservoirs and polymeric dispersed systems are in development for intravitreous slow release of drugs and proteins • Few drug delivery systems cross the clinical stage due to insufficient multidisciplinary development • Fundamental work is still required to build guidelines for toxicity and models for ocular pharmacokinetic studies.

Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects

“…Biomedicines 2021, 9, 341 4 conjunctivitis, and dry eye) and the posterior (choroiditis, uveitis, age-related macula generation, diabetic macular edema, and diabetic retinopathy) segments [5,7,[65][66][67][68][69][70][71] The pharmacokinetics and pharmacodynamics parameters of DEX indicate tha development of modified DEX nanodrugs is relevant primarily for topical administr (such as ophthalmic and dermal) and other application routes (such as intravitrea traarticular, inhalation, nasal, and otic). The use of various nanocarriers for these typ administration would therefore focus on increasing the drug residence time at the t site through bio-adhesion, as well as on providing a controlled sustained release.…”

“…DEX is used to treat many conditions, including rheumatoid arthritis, bronchial asthma, systemic lupus erythematosus, autoimmune diseases, shocks of various etiologies, skin allergic diseases (neurodermatitis, eczema), and chronic rhinosinusitis, as well as to suppress transplant graft rejection [5,18,34,[56][57][58][59][60][61][62][63][64]. DEX readily penetrates the conjunctiva, so it is one of the most commonly used GCs for the treatment of ocular conditions, including inflammation diseases of both the anterior (keratitis, blepharitis, allergic conjunctivitis, and dry eye) and the posterior (choroiditis, uveitis, age-related macular degeneration, diabetic macular edema, and diabetic retinopathy) segments [5,7,[65][66][67][68][69][70][71].…”

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

“…CS and its derivatives have demonstrated safety and satisfying biocompatibility following intravitreal injections on in vivo models [34][35][36][37]. DEX was chosen as the test drug because it is a high-efficacy synthetic glucocorticosteroid (7 times more potent than prednisolone) and one of the most frequently used anti-inflammatory drugs for the treatment of eye disease, including inflammatory diseases of both the anterior (e.g., keratitis, blepharitis, allergic conjunctivitis, and dry eye) and posterior (e.g., choroiditis, uveitis, age-related macular degeneration, diabetic macular edema, and diabetic retinopathy) segments [38][39][40].…”

Preclinical challenges for developing long acting intravitreal medicines

“…14 Reduced compliance after the first year of treatment has also become evident, [16][17][18] especially for patients that have not previously been part of a clinical trial. 19,20 There have been efforts to use antibodies systemically to treat ocular inflammatory conditions such as uveitis, 21 however, systemic administration requires high doses for most drugs to be present intraocularly, resulting in the exposure of non-target tissues and dose limiting side effects. 2 Systemically administered drugs, such as tablets, must overcome the blood-retina barrier (BRB), and this usually results in low intraocular drug concentrations, due to an inability to penetrate the BRB.…”