Dispersion of Nanoparticles in Hydrogels for Ophthalmic Drug Delivery

University Of Florida, Gainesville FL

Investigators

Abstract

ABSTRACT - 0426327 Dispersion of Nanoparticles in Hydrogels for Ophthalmic Drug Delivery Approximately 90% of all ophthalmic drug formulations are now applied as eye-drops1. While eye-drops are convenient and well accepted by patients, a majority of the drug contained in the drops is lost due to tear drainage. The drops mix with the tear fluid, and subsequently, about 95% of the drug flows through the upper and the lower canaliculi2. Eventually, a major portion of the drug is absorbed in the nasolacrymal duct, and enters the blood stream. This can lead to serious side effects. For instance, absorption of Timolol, a beta-blocker used to treat glaucoma, has harmful effects on the heart3. Furthermore, topical ophthalmic drug delivery results in a relatively high drug concentration in the tear film followed by a rapid decline. This causes sharp variations in the drug delivery rates to the cornea that reduces the efficacy of ophthalmic drugs4. Intellectual Merit: To reduce drug loss, eliminate systemic side effects, and improve drug efficacy, we propose to develop disposable soft contact lenses as a new vehicle for ophthalmic drug delivery. The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles, and to disperse these drug-laden particles in the lens material. This work focuses on soft lenses made of poly 2-hydroxyethyl methacrylate (HEMA) hydrogel. The hydrogel matrix of HEMA lenses is synthesized by bulk or solution polymerization of HEMA monomers in the presence of a cross linker such as ethylene glycol di-methacrylate (EGDMA)5. Addition of drug-laden particles in the polymerizing medium results in the formation of a particle-dispersion in the hydrogel matrix. If a contact lens made of this material is placed on an eye, the drug diffuses from the particles, and through the lens matrix, and enters the thin tear film trapped between the cornea and the lens. The three specific objectives of the study are, (i) encapsulate ophthalmic drugs in nanosized colloidal particles and study the stability of these particles, (ii) incorporate the drug-laden particles in the hydrogel matrix during the polymerization process, and study the microstructure and the physical properties of the particle-laden gel, and (iii) measure and model the drug release rates from the particles and the hydrogel to determine the controlling mechanism, and eventually control the release rates from the hydrogel by manipulating the particle and/or gel properties. We have successfully fabricated transparent gels loaded with two different types of particles: microemulsion drops and liposomes. We have also established that contact lenses fabricated from the particle laden gels can deliver ophthalmic drugs at therapeutic rates for a few days. The proposed future work focuses on advancing the fundamental knowledge of particle entrapment, aggregation, segregation, controlling mechanisms of drug transport, and fluid mechanics of the human eye. In addition we wish to increase drug loading and improve the drug release profiles to obtain zero order delivery rates, and also develop the optimal systems for various ophthalmic drugs. Broader Impact: Drug delivery is rapidly becoming a very important research area due to its enormous societal impact. This field has the potential to significantly improve the quality of life, save lots of lives, and offer improved treatment for a number of diseases. Our proposed research will help deliver ophthalmic drugs in an efficient and controlled manner that could potentially reduce drug wastage, improve compliance, minimize side effects and maximize the efficacy of currently available drugs. Drug delivery through contact lenses could be very useful for patients suffering from glaucoma because use of beta-blockers to treat this disease has serious side effects on heart. Furthermore due to the rapidly increasing importance of drug delivery, it is important to expose students to this area of research as early in their careers as possible. To achieve this objective, the PI proposes to include gel fabrication and drug delivery through gels in Transport and Interfacial Phenomena classes and involve undergraduate students in the research.