(548d) Highly Crosslinked Microparticles and Dispersions of the Particles in Polymers for Extended Drug Delivery

The drug release timescales need to be controlled for a number of biomedical applications such as ophthalmic drug delivery. Ophthalmic drug delivery via eye-drops is inefficient because of low bioavailability of 5% or less. Ophthalmic drug delivery by contact lenses has a bioavailability of about 50%, so use of contact lenses for drug delivery can minimize drug loss and the associated side effects, and also lead to higher compliance. However commercial contact lenses are not suitable for delivering ophthalmic drugs because these release drugs only for a short period of abut 1-2 hours. This talk will focus on dispersing highly crosslinked microparticles in polymeric contact lenses to increase the duration of drug release from 1-2 hours to about 1-2 weeks.

The highly crosslinked particles were prepared by emulsion polymerization of a monomer with multivinyl functionalities (ex. EGDMA (ethylene glycol dimethacrylate), PGT (propoxylated glyceryl triacylate)) leading to a highly crosslinked structure. The base form of timolol, a glaucoma drug, was added to the monomer and so it was trapped in the microparticles. The drug loaded particles were then dispersed in various polymers suitable for contact lenses including hydroxy methyl methacrylate (HEMA) and silicone hydrogels.

The particle-laden are transparent, and release drug slowly for an extended period ranging from 2-3 weeks at therapeutic doses. The proposed mechanism of drug transport is a short-time burst due to diffusion of drug from the bulk matrix, followed by an extended release from inside the particles. The mechanisms of transport were established by measuring transport in particle-laden gels of various thicknesses. The duration of the burst phase is proportional to the square of the thickness and the slow release is independent of the thickness, proving the mechanisms proposed above. The mechanical properties of the particle-laden lenses were measured and it was shown that although the modulus of the lenses increase, the lenses are still suitable for use. Also particles were prepared with a mix of the multi-vinyl functionality monomer and hydrophobic additives such as Vitamin E, methyl methacrylate, silicone monomers to control the degree of crosslinking and hence the release rates.

The results of this talk provide evidence that contact lenses loaded with microparticles could be very useful for extended delivery of ophthalmic drugs. Additionally, addition of highly crosslinked microparticles to polymers in general could be an effective method for manipulating release profiles without impacting the bulk properties.