Self-assembled γ-cyclodextrin as nanocarriers for enhanced ocular drug bioavailability

Cyclodextrins (CDs) are widely used in pharmaceutical products for improving the solubility and bioavailability of drugs through the formation of water-soluble inclusion complexes. Among natural CDs, γ-cyclodextrin (γCD) has the highest water solubility, largest cavity size, and most favorable toxicological profile. γCD can form inclusion complexes with a wide variety of drugs. In aqueous solution, γCD tends to self-assemble to form aggregates, leading to formation of both nano- and microparticles. The self-assembled γCD molecules can increase the solubility and enhance drug permeability through biological membranes, consequently improving drug bioavailability. This promising drug delivery platform is well tolerated, and it has low ocular toxicity. Clinical studies have shown that this nanocarrier can enhance topical drug delivery to both the anterior and posterior segment of the eye. The present article reviews the physicochemical properties of γCD and its derivatives, their toxicological profiles, the γCD solubilization of drugs, and methods for enhancing drug/γCD complexes and their aggregates. Additionally, examples of self-assembled drug/γCD complexes in ophthalmic preparations are discussed.