Temperature sensitive contact lenses for triggered ophthalmic drug delivery

Abstract

Ophthalmic drug delivery through eye drops is inefficient because of low corneal bioavailability and short residence time in tears. Contact lenses are ideally suited for extended and targeted drug delivery to cornea, but commercial contact lenses release ophthalmic drugs for only 1-2 h. This study focuses on dispersing timolol encapsulating highly crosslinked nanoparticles in contact lenses to increase the duration of drug release from 1 to 2 h to about 2-4 weeks. The highly crosslinked particles were prepared from monomers with multivinyl functionalities such as EGDMA (ethylene glycol dimethacrylate) and PGT (propoxylated glyceryl triacylate). The nanoparticles were about 3.5 nm in size and encapsulated 48-66% of the drug depending on the composition. Drug release studies in a diffusion cell showed that the particles released the drug for a period of about 4 weeks. The drug loaded particles were dispersed in hydroxy methyl methacrylate (HEMA) gels, which are common contact lens materials. The particle loaded gels release timolol in phosphate buffered saline (PBS) for 2-4 weeks at therapeutic dose, which is promising for extended drug release applications. The proposed mechanism of drug transport is hydrolysis of ester bonds that link timolol to the particle matrix which form during the particle formation process. The drug release profiles can be described by a first order reaction model with a temperature dependent rate constant. The rate constant of ester hydrolysis was significantly smaller than that in previous studies on timolol esters possibly due to steric effects and the low water content of the highly crosslinked hydrophobic particles. The results of this study provide evidences that contact lenses loaded with nanoparticles could be very useful for extended delivery of ophthalmic drugs.