382732 Ophthalmic Drug Delivery By Contact Lenses
Conventional ophthalmic drug by eye drops is very inefficient with a low bioavailability of 1-5% due to the short residence time of about 5 min in the eyes, and the loss of the drug across the conjunctiva. We have shown, both through mathematical modeling and animal models, that the corneal bioavailability can be increased to about 50% by using drug eluding contact lenses. Currently available commercial contact lenses are, however, not optimal for drug delivery due to the very short release duration of about an hour for most ophthalmic drugs. Our lab has focused on developing contact lenses that can deliver ophthalmic drugs for significantly longer durations compared to commercial lenses, but without sacrificing any of the critical optical, mechanical or transport properties.
This talk will describe the following five approaches that we have developed for extended release of drugs from contact lenses:
1. Self assembled vesicles,
2. Ionic surfactants,
3. Polymeric nanoparticles chemically linked to the drugs,
4. Diffusion barriers and
5. New silicone hydrogel materials.
Some of these approaches can be adapted to modify lenses after polymerization, so commercial contact lenses can be modified to increase the drug release duration. The release duration of drugs from the lenses depends on the physical properties but, in general, we can increase the release duration by at least a factor of 100 compared to the commercial lenses. For some drugs, we have succeeded in increasing the drug release duration to as long as a few months. The drugs of interest include timolol, dorzolamide, latanoprost, cysteamine, dexamethasone, dexamethasone phosphate, cyclosporine, lidocaine, fluconazole, etc. In vitro results will be presented to show the drug release profiles and also to show that the designed lenses retain all critical properties necessary for extended wear including transparency, ion and oxygen permeability, modulus, water content, wettability, etc. Some of the approaches described above improve several other properties in addition to drug release profiles, including wettability, UV blocking, etc.
We have successfully conducted animal studies in Beagle dogs with lenses loaded with vitamin E diffusion barriers and nanoparticles with a chemically attached drug. These studies demonstrated that drug eluding contact lenses can reduce the intra ocular pressure significantly even when the amount of drug loaded in the lenses is significantly smaller than that in drops. We also compared several different drug delivery approaches including eye drops, commercial lenses and vitamin E loaded lenses with vitamin E. Results showed that continuous wear of lenses loaded with about 20% vitamin E is safe and can reduce the IOP during the entire wear time. Eye drops administered daily can also reduce the IOP, but the amount of drug delivered through the eye drops is about six times that delivered through the vitamin E loaded contact lenses. Commercial contact lenses without vitamin E replaced daily can also achieve therapeutic IOP reduction but these lenses cannot achieve significant IOP reduction for long durations. We also demonstrated that the extended delivery of drugs from contact lenses can achieve therapeutic reduction in the IOP for durations significantly longer than the wear duration through creation of drug depots in the eyes. This opens the possibility of achieving continuous therapeutic effects with intermittent use of the lenses.