Table 3.

Advantages and disadvantages of different delivery systems for back-of-the-eye delivery of biologics

Delivery System	Advantages	Disadvantages	Ref
Conventional	Patient compliance. Easily administered	Rapid pre-corneal elimination Blurred vision Unable to cross ocular barriers to the back of the eye Poor bioavailability	[3,138]
Vesicular	Biocompatible, biodegradable, safe materials can be used. Can encapsulate hydrophilic and hydrophobic drugs. Can sustain release of encapsulated drug	Oxidative degradation of phospholipids. Instability e.g. liposomes. Large size e.g. discosomes Non patient compliance	[3,139] [19]
Particulate	Biocompatible, biodegradable, non-toxic materials. Control and prolonged release of therapeutic molecules. High bioavailability to the target site. Different routes of administration. Large drug payload e.g. lipid nanoparticles	Patient non-compliance Associated with IOP, retina hemorrhage, retinal detachment, and endophthalmitis. Initial burst release of drugs Degradation of specific polymers may results to lower pH, hence irritation. Poor stability of macromolecules Low encapsulation efficiency	[25,140–143] [144,145]
Control Release	Control and sustained release of therapeutic molecules. Various routes of administration can be applied. High bioavailability of therapeutic molecules to the target site Control of IOP Improved patient compliance e.g. implants	Replacement of the unit in case of contamination or depletion of the active agent. Might require a medical personnel and surgery to insert and remove the device e.g. implants. Education to handle and clean e.g. contact lenses Active agent might not able to cross ocular barrier to the posterior segment in case of contact lenses. Costly	[146–150]
Advanced	No toxicity, safe Stable Enhanced bioavailability Rapid drug delivery Tissue targeting Possibility of treating vascular and neuronal ocular diseases	Immune responses Random integration Vehicle selection can be challenging Poor cell permeability and degradation of nucleases Intracellular and extracellular barriers	[141,151–154]