Recent advances in ocular drug delivery systems and targeting VEGF receptors for management of ocular angiogenesis: A comprehensive review

Abstract

Background Angiogenic ocular diseases address the main source of vision impairment or irreversible vision loss. The angiogenesis process depends on the balance between the pro-angiogenic and anti-angiogenic factors. An imbalance between these factors leads to pathological conditions in the body. The vascular endothelial growth factor is the main cause of pathological conditions in the ocular region. Intravitreal injections of anti-angiogenic drugs are selective, safe, specific and revolutionized treatment for ocular angiogenesis. But intravitreal injections are invasive techniques with other severe complications. The area of targeting vascular endothelial growth factor receptors progresses with novel approaches and therapeutically based hope for best clinical outcomes for patients through the developments in anti-angiogenic therapy. Main text The present review article gathers prior knowledge about the vascular endothelial growth factor and associated receptors with other angiogenic and anti-angiogenic factors involved in ocular angiogenesis. A focus on the brief mechanism of vascular endothelial growth factor inhibitors in the treatment of ocular angiogenesis is elaborated. The review also covers various recent novel approaches available for ocular drug delivery by comprising a substantial amount of research works. Besides this, we have also discussed in detail the adoption of nanotechnology-based drug delivery systems in ocular angiogenesis by comprising literature having recent advancements. The clinical applications of nanotechnology in terms of ocular drug delivery, risk analysis and future perspectives relating to the treatment approaches for ocular angiogenesis have also been presented. Conclusion The novel ocular drug delivery systems involving nanotechnologies are of great importance in the ophthalmological sector to overcome traditional treatments with many drawbacks. This article gives a detailed insight into the various approaches that are currently available to be a road map for future research in the field of ocular angiogenesis disease management.

Ocular Delivery of Therapeutic Proteins: A Review

“…The topical route is preferred for the delivery of drugs to the anterior chamber of the eye for the treatment of cataract, dry eye, and corneal and conjunctival inflammatory and infectious diseases [ 37 ]. The topical ocular delivery route is not commonly used for the delivery of therapeutic proteins for retinal tissues due to the presence of ocular barriers; only <5% of the instilled dose enters through anterior segment to the posterior segment via the tear film and cornea (epithelium, endothelium, and stroma) to the anterior chamber of the eye [ 8 , 9 , 10 , 38 , 39 ]. The extent of absorption of drug molecules from the corneal surface is severely limited by different physiological barriers, such as:…”

“…A usual practice is to combine technologies, such as injectable hydrogels containing nano- or microparticles, liposomes, or nanoparticles containing therapeutic proteins coated with bioadhesive polymers [ 8 , 9 ]. Advantages of sustained delivery of therapeutic protein formulations include improved patient compliance, adherence to chronic therapy, and local delivery with fewer side effects and a reduction in dosage and dosing frequency [ 10 ].…”

Considerations for Polymers Used in Ocular Drug Delivery

“…PRINT R has been used to develop subconjunctival implants, intracameral implants, intravitreal implants, nano-and micro-suspensions, etc (190). One recent development with PRINT R technology is the AR13503 (Aerie Pharmaceuticals) implant, which utilizes PLGA, PDLA, and PEA to control delivery to the retina for more than 2 months and is in phase 1 clinical trials (190)(191)(192)(193). Another delivery system developed with PRINT R is an Envisia Therapeutics implant (ENV515) currently in phase 2 clinical trials (194).…”

Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats

“…The implant area should be activated by angiogenic growth factors to avoid vascular complications and stimulate new tissue growth [ 4 , 5 ]. Targeted delivery and release of pro-angiogenic molecules is one of the key challenges in precision medicine [ 6 , 7 , 8 ]. One of the solutions to improve the rate of vascularization is biological modification of a graft with biomolecules and cells [ 9 , 10 ], which may lead to a reduction in inflammation and ischemia in affected tissues [ 11 , 12 ].…”