(2b) Bandage Contact Lenses for Anti-Inflammatory Therapeutics | AIChE

(2b) Bandage Contact Lenses for Anti-Inflammatory Therapeutics

Authors 

Zhang, J. - Presenter, Auburn University


The US ophthalmic drug market is valued at approximately $4.5 billion and conventional topical ocular therapies control approximately 90% of that market, with inflammation treatments accounting for 55% or $2.5 billion. However, there is still an unmet need in the ocular therapeutic market for effective drug delivery. A major obstacle facing traditional topical methods of ocular drug delivery is poor bioavailability with only 1-7% of the applied drug absorbed while the rest is either removed by the lacrimal and tear turnover or enters into systemic circulation. We have rationally designed and synthesized novel contact lenses capable of tailorable loading and extended release of anti-inflammatory ocular medication.

This novel drug delivery system will deliver ocular medication via contact lenses in which the drug is released from the hydrophilic, weakly cross-linked polymers of the lens directly onto the surface of the eye. These recognitive polymers are synthesized via a biomimetic imprinting technique, which allows for the formation of pre-polymerized complexes between the drug molecule and functional monomers that are chosen with specific structures designed to interact with the drug molecule via non-covalent chemistry. The polymers were synthesized with a cocktail of FDA-approved methacrylate and acrylate monomers that provided similar side-chain functionalities to amino acids present in the binding pockets of the biomolecules as found in nature. Hydrogels were synthesized with macromolecular ?memory? site or reservoirs for the non-steroidal anti-inflammatory drug diclofenac salt.

These biomimetic contact lenses exhibited the ability for biomolecule recognition and memory and demonstrated advantage over hydrogels created without biomimesis by displaying a two-fold increase in drug loading. Further binding studies were conducted with the addition of iniferter to the polymer formulation to reversibly terminate the UV free radical polymerization. The addition of iniferter to the recognitive system created a two-fold increase in loading over the recognitive system without iniferter due to formation of more ordered and uniform crosslinked polymer network. Equilibrium swelling studies indicated that 40% of the swollen gel is water, indicating the adequate comfort of wearing and oxygen permeability of these gels. Dynamic drug release profiles demonstrated that release rates for the biomolecule in the recognitive systems can be tailored to provide a sustained release in artificial lacrimal fluid. The diffusion coefficient calculated for the recognitive system was an order of magnitude lower than that of the control system, demonstrating that imprinting extends the release rate with greater functionality leading to greater delay in release. Further diffusion analysis revealed that while the control system was exhibiting Fickian release profile, driven by pure diffusion, both the recognitive and iniferter systems exhibited release profiles closer to zero-order, constant release. Parametric studies to optimize loading and extend release were performed by synthesizing hydrogels with varying monomer to template ratios. Furthermore, these hydrogels presented the same ocular clarity and mechanical functionalities as conventional contact lenses and could also offer the same comfort and tissue re-epithelialization properties as hydrophilic bandage contact lenses (HBCLs), which provide a mechanical barrier against the shearing forces of eye lids and can act as a hydrating reservoir.