Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Abstract

Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.These authors contributed equally: Ivan Seah Yu Jun, Zhao Xin Xin 1234567890();,:1234567890();,:

Nanoparticle-Hydrogel Composite Drug Delivery System for Potential Ocular Applications

“…As a result, many studies have used PLGA as a drug carrier for various types of therapy, including protein drug therapy [ 22 , 23 , 24 ]. In particulate DDS, particle size can affect the drug loading amount, drug release rate, biocompatibility, and the ability of the particles to penetrate tissues [ 25 ]. Although smaller particles have lower drug loading amounts than larger particles, they provide higher tissue penetration [ 25 ].…”

“…In particulate DDS, particle size can affect the drug loading amount, drug release rate, biocompatibility, and the ability of the particles to penetrate tissues [ 25 ]. Although smaller particles have lower drug loading amounts than larger particles, they provide higher tissue penetration [ 25 ]. Particles with a diameter of <200 nm have been proved to penetrate from vitreous to retinal layers, which can further prolong the half-life of the NPs in the vitreous humor [ 26 ].…”

“…These hydrogel networks provide a hydrophilic environment for the stable storage of protein drugs, cells, and nanoparticles by preventing them from enzymatical degradation and hydrophobic interaction, which may harm the cargos [ 28 , 29 ]. In addition, the porous structure of the hydrogels supports a high payload of the contents [ 25 ]. Hydrogels can be made of natural polymers [ 30 , 31 ], synthetic polymers [ 32 , 33 ], or a combination of the two [ 11 ].…”

“…Hydrogels can be made of natural polymers [ 30 , 31 ], synthetic polymers [ 32 , 33 ], or a combination of the two [ 11 ]. Natural polymers tend to be more degradable than synthetic ones since they have more hydrolysable linkages and can be subjected to enzymatic degradation within a living body [ 25 ]. For drug delivery to the posterior segment of the eye, injectable hydrogels are preferred due to the minimally invasive method required to transport them to the vitreous humor.…”

Efficient Gene Delivery Based on Guanidyl‐Nucleic Acid Molecular Interactions

“…First, dilution in local tissue by interstitial fluid leads to rapid elimination of gene complexes at the administration site. [ 12 ] Second, the amphiphilic cell membrane inhibits entry of gene complexes into the cytosol. [ 13 ] Third, degradation by lysosomal enzymes and obstruction by the nuclear membrane also decrease the transfection efficiency of gene complexes.…”