Ocular Drug Delivery
Research in Dr. Ravi’s laboratory is directed toward understanding the pathophysiology of presbyopia and developing medical or surgical treatments for this condition. Presbyobia, which means “aging eye,” results in an inability to see clearly at near distances. Although this condition is not vision threatening, it affects all of us. The current treatment for this condition is bifocals, which provides good vision at only two focal planes. Benjamin Franklin first created bifocals more than 200 years ago. Our research lab is investigating the lens-based causes of presbyopia by quantifying the biomechanical behaviors of the lens. We use these measurements to reverse engineer potential lens prostheses by designing novel polymeric. A key challenge is to identify materials that not only match the human lens in physical, optical, and mechanical properties, but that also exhibit biocompatibility and long term stability. These substances should also be introduced into the eye by a minimally invasive surgery. We have identified copolymers that can potentially be injected into a pre-evacuated lens capsular bag, wherein they can spontaneously form a gel.
The vitreous body is the clear “jelly” in the middle of the eye behind the lens. It is approximately 99% water by weight, with the remainder primarily crosslinked type II collagen fibrils and hyaluronic acid. It acts as a viscoelastic damper during eye movements, thus ensuring retinal attachment to choroid. With advancing age, the vitreous undergoes a non-uniform transition from a formed gel to a phase separated fluid in an elderly adult, leading to the appearance of “floaters.” A number of vision-threatening phenomena such as macular holes, retinal detachments, and vitreous hemorrhage are associated with this transition. Clinically, silicones and perflorocarbons are used as temporary vitreous substitutes. However, we have designed, synthesized, and characterized water soluble copolymers that, upon injection within the vitreous cavity, spontaneously form a hydrogel under certain physiological conditions. The formed hydrogel is optically clear, contains more than 95% water, matches the viscoelastic properties of the natural vitreous, and exhibits minimum toxicity in both tissue culture and rabbits. Various polymers are being synthesized and tested for improved properties as a vitreous substitute.
The perception of vision and the ability to dynamically focus are excellent examples of how nature exploits nanoscience. The cornea, lens, and vitreous efficiently utilize nanoscience to perform their functions. We have designed and synthesized nanogels to mimic the properties of globular lens proteins called crystallins. These nanogels closely match the crystallins’ size, viscoelasticity, and refractive index (RI). We are also investigating the role of quantum dots for use as artificial retina.
We have developed techniques of making nanoparticles using block-copolymers that have tissue adhesive properties. Pilocarpine was used as a prototypic drug. Thermodynamic polymer-drug interaction calculations are also performed.
Dr. Ravi has over 100 publications, including papers, abstracts and 4 book chapters. He holds 8 patents and has delivered over 50 invited lectures. A few current and relevant publications are listed below
- Hamilton PD, Jacobs DZ, Rapp B, Ravi N, 2009: Surface Hydrophobic Modification of Fifth-Generation Hydroxyl-Terminated Poly(amidoamine) Dendrimers and Its Effect on Biocompatibility and Rheology. Materials 2(3): 883-902.
- Reilly M.A., Ravi N, 2009: Microindentation of the Young Porcine Ocular Lens. Journal of Biomechanical Engineering, 131:044502.
- Reilly M, Hamilton PD, Perry G, Ravi N, 2009: Comparison of the Behavior of Natural and Refilled Porcine Lenses in a Robotic Lens Stretcher: Experimental Eye Research, 88(3): 483-494.
- Swindle KE, Hamilton PD, Ravi N, 2008: In situ formation of hydrogels as vitreous substitutes: viscoelastic comparison to porcine vitreous. Journal of Biomedical Materials Research Part A. 87A-3: 656-665.
- Rapp B, Reilly MA, Hamilton PD, Shen A, Ravi N, 2008: Material Characterization of Porcine Lenticular Soluble Proteins. Biomacromolecules, 9(6):1519-1526.
- Reilly MA, Hamilton PD and Ravi N, 2008: Novel Dynamic Multi-Arm Radial Lens Stretcher: A Mechanical Analog of the Ciliary Body. Experimental Eye Research, 86:157-164.
- Andley U, Hamilton PD, Ravi N, 2008: Mechanism of Insolubilization by a Single point Mutation in αA-Crystallin Linked with Hereditary Human Cataract. Biochemistry, 47 (36): 9697–9706.
- Swindle KE, Ravi N, 2007: Recent Advances in Polymeric Vitreous Substitutes. Expert Rev. Ophthalmol. 2(2): 255-266.
- Foster WJ, Aliyar, HA, Hamilton PD, Ravi N, 2006. Internal Osmotic Pressure as a Mechanism of Retinal Attachment in a Vitreous Substitute. J. Bioact. Compat. Polym. 21(3): 221-235.
- Ravi N, Aliyar H, Hamilton PD, 2005: Hydrogel nanocomposite as a synthetic intra-ocular lens capable of accommodation, Macromol. Symp. 227(1): 191-202.