Table 1. . Physiological challenges to ocular drug delivery.

Challenges	Effect	Ref.
Anatomy and physiological limitations	• Reduced precorneal residence time • Frequent dosing required; leading to a reduced patient compliance • Nasolacrimal drainage leads to drug loss • Systemic toxicity • Ocular toxicity	[43–64]
Physicochemical limitations	• Reduce transcorneal flux • Poor drug solubility and permeability • Drug storage instability leading to reduced efficacy and increased cost	[52,54–55,65–67]
Ocular and systemic toxicities	• Damage to the ocular tissues (retinal necrosis, loss of retinal ganglion cells, vitreous inflammation, corneal edema, neovascularization and inflammation) and occurrence of systemic toxicities (hepatotoxicity and nephrotoxicity) and side effects (gastrointestinal disturbances) observed.	[43,49–52,59,61–64,68–78]