(303b) Using a Mathematical Model to Quantify Drug Release from an Ocular Lens Delivery System Loaded with Nanoparticles

Non-invasive drug delivery to the eye has been limited mainly to the use of eye drops, which is inefficient for the treatment of diseases affecting the innermost layers of the eye such as the retinal endothelium. This is because only 5 % of the drug in eye drops penetrates the cornea of the eye, as most of it is washed out by tears. Alternatively, the use of ocular inserts and injections into the eye are invasive techniques, which meet with low patient compliance. These inserts are surgically placed in the targeted area, releasing the therapeutic amount of drug over the required period.  Contact lens delivery systems show burst releases of drug followed by low release profiles over extended periods.  New drug delivery methods to the eye are needed to treat diseases such as diabetic retinopathy, glaucoma and age-related macular degeneration. Drug‑loaded nanoparticles are possible vehicles of targeted drug delivery to the interior of the eye since they are small enough to penetrate the various membranes present in the eye. 

Our group has developed a non-invasive method of controlled drug delivery to the eye. The system consists of drug-loaded PLGA nanoparticles embedded in a thin collagen membrane. The nanoparticle-loaded membrane may be placed on the inside of a commercial contact lens for support and to ensure constant contact of the membrane with the cornea for an extended period. This allows penetration of the particles and drug into the innermost layers of the eye, such as the retina. Lidocaine was used as a hydrophobic, small molecule model drug to test the system. PLGA has been used since it is biocompatible and biodegradable, and degrades on contact with the enzymes present in the eye, allowing controlled release of lidocaine over extended periods. The collagen membrane controls the burst release of the drug from the nanoparticles thereby allowing therapeutic release over a longer period. The morphology and release profiles of both the nanoparticles and the nanoparticle‑loaded membrane have been studied.

The objective of this work was to develop a mathematical model to describe the release of lidocaine from the proposed drug delivery system consisting of drug-loaded nanoparticles embedded in a collagen matrix. The basis of this model is that drug is released from PLGA nanoparticles through diffusion as well as erosion of the polymer and into the collagen matrix. The released drug diffuses through the collagen membrane and into the eye. Diffusivities of lidocaine through PLGA and collagen were obtained experimentally. Experimental results of release studies through the nanoparticle-loaded collagen matrix were used to obtain the partition coefficient of lidocaine in PLGA/collagen. The model equation predicts the release of lidocaine from the complete system and shows the influence of key design parameters such as diffusivity of lidocaine through PLGA and collagen, rate of particle degradation, diffusion of nanoparticles through the collagen membrane, interaction of collagen with lidocaine, and the partition coefficient of lidocaine between PLGA and collagen during drug release from the system.