ABSTRACT
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To date, nearly all ocular therapeutics have been administered to the eye as simple aqueous
solution eyedrops by instillation to the lower conjunctival sac. The main drawbacks of
aqueous eyedrops are their inability to deliver lipophilic and insoluble molecules, their low
retention time, and their limited ability to resist the washout effect of blinking and tears
turnover. The expected 10% to 20% fraction of the applied topical dose that escapes the
immediate washout by blinking and tearing is then challenged by tear fluid proteins and
enzymes binding and metabolism, ocular permeation barriers, phagocytic activity and partial
diversion to adjacent tissues, and systemic circulation. Thus, more drug elimination occurs
before it reaches the target tissue. Therefore, it is estimated that only 1% or less of the
administered dose can penetrate the ocular surface [1,2]. Moreover, when targeting a remote
target tissue like the retina, the fraction of the administered dose that reaches the action
site will be much less due to further anatomical barriers, aqueous humor turnover, intraocular
metabolic activity, binding to intraocular pigmented tissues, and phagocytosis by cell line
other than the targeted tissue cells.
