Therapeutic contact lenses for extended drug delivery

Thumbnail Image
Publication or External Link
Torres Luna, Cesar Eduardo
Wang, Nam Sun
Briber, Robert M
There is significant interest in hydrogel-based drug-eluting contact lenses as platforms for topical ocular drug delivery. These devices have shown to provide an increased residence time of drugs at the surface of the eye, leading to enhanced bioavailability (~ 50%) when compared to eye drops (1–5%). One major limitation of contact lenses for drug delivery is that most drugs are released in a few hours, which limits their application for extended delivery. In this dissertation, we develop novel drug-eluting contact lenses that are capable of achieving extended in vitro drug delivery. In our first study, we describe the application of drug-participating catanionic aggregates in poly-(2-hydroxy-ethyl-methacrylate) based contact lenses. Contact lenses embedded with catanionic aggregates can achieve extended delivery of at least 1-week for two anionic drugs. Release kinetics is significantly dependent on the drug’s octanol-water partition coefficient, the hydrocarbon chain length and concentration of the cationic surfactant. Next, we focus on the use of unsaturated fatty acids in commercial contact lenses to extend the release of three cationic drugs. We demonstrate that lenses loaded with oleic acid can extend drug release kinetics to over 1 month. An opposite effect is seen for two anionic drugs, where oleic acid significantly accelerates release kinetics. These studies confirm the dominating impact of coupling charge interactions between drug molecules and fatty acid carrier molecules in contact lenses to adjust drug delivery rates. Finally, we extend the application of fatty acids in contact lenses to evaluate the effect of hydrocarbon chain length, ionic strength, and pH on the release kinetics. It is shown that fatty acids with carbon chain lengths equal or greater than 12 are capable of extending drug release of two cationic drugs, which confirms the importance of hydrophobic interactions with the silicone domain of the gel matrix. By decreasing ionic strength (from 1665 to 167 mM) or increasing the pH of the release media (from 5.5 to 7.4), release kinetics is significantly extended. In summary, the use of fatty acids to control the release of oppositely charged drug molecules represents a versatile tool to modify contact lenses for drug delivery applications.