Role of Polymeric Micelles in Ocular Drug Delivery: An Overview of Decades of Research

Abstract

Local drug delivery to the eye through conventional means has faced many challenges due to three essential barriers: (a) the complex structure of the cornea limiting drug absorption, (b) the capacity of ocular absorptive cells in drug metabolism, and (c) the washing effect of eye tears. Polymeric micelles (PMs) have been the focus of much interest for ocular drug delivery due to several advantages they provide for this application, including the capacity for the solubilization of hydrophobic drugs, nonirritability, nanoscopic diameter, and the clarity of their aqueous solution not interfering with vision. The potential to increase the release and residence time of incorporated medication at the site of absorption is also a bonus advantage for these delivery systems. This Review covers research conducted on single or mixed micelles prepared from small amphiphilic molecules, copolymers (diblock, triblock, and graft), and gel systems containing micelles. The purpose of this review is to provide an update on the status of micellar ocular delivery systems for different indications, with a focus on preclinical and clinical drug development. In this context, we are discussing the anatomy of the eye, various ocular barriers, different micellar formulations, and their benefits in ocular drug delivery, as well as the role of PMs in the management of ocular diseases both in preclinical models and in clinic. The encouraging preclinical effectiveness findings from experiments conducted in both laboratory settings and live animals have paved the way for the advancement of micellar systems in clinical trials for ocular administration and the first nanomicallar formulation approved for clinical use by the United States Food and Drug Administration (marketed as Cequa by Sun Pharmaceuticals).

Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery

“…The ciliary body is positioned behind the iris and produces aqueous humor, which provides nutrition to the internal structures of the eye [ 14 ]. The produced aqueous humor moves toward the cornea, collects within the Schlemm’s canal, and empties into the episcleral blood vessels [ 14 ]. Consequently, the aqueous humor acts as a dynamic barrier to removing therapeutic drugs from the ocular structures [ 14 ].…”

“…The produced aqueous humor moves toward the cornea, collects within the Schlemm’s canal, and empties into the episcleral blood vessels [ 14 ]. Consequently, the aqueous humor acts as a dynamic barrier to removing therapeutic drugs from the ocular structures [ 14 ]. The rapid turnover of aqueous humor further diminishes the concentration of the medicines, exacerbated by resistance to the direction of aqueous humor flow [ 14 ].…”

“…Consequently, the aqueous humor acts as a dynamic barrier to removing therapeutic drugs from the ocular structures [ 14 ]. The rapid turnover of aqueous humor further diminishes the concentration of the medicines, exacerbated by resistance to the direction of aqueous humor flow [ 14 ]. As drugs gradually migrate from the aqueous humor to the posterior compartment, they contact the iris and lens.…”

“…As drugs gradually migrate from the aqueous humor to the posterior compartment, they contact the iris and lens. Knowledge from the literature indicates that the ciliary body and iris express specific active drug transporters, thereby hindering the permeation of drugs [ 14 ]. Moreover, the melanin pigment in the ciliary body attaches to the drug, and the iris can obstruct the drug from reaching the posterior compartment [ 14 ].…”

“…The sclera poses a major challenge in ophthalmic drug delivery with its limited permeability [ 14 ]. The sclera comprises a dense, hydrophilic, collagenous connective tissue that makes up the outer shell of the eyeball [ 14 ].…”