Age Related Macular Degeneration (AMD) is the leading cause of blindness in adults over 50 years. Choroidal neovascularization (CNV), the pathologic creation of new blood vessels in the choroid layer of the eye, is a principal cause of blindness due to AMD. Current therapeutic management of AMD is far from optimal and requires repeated injections in the vitreous cavity of the eye. Such repeated administrations, besides being inconvenient for the patient, might lead to retinal detachment and endophthalmitis. Thus, there is an unmet need to develop delivery systems which can be administered by relatively safer routes of administration such as topical dosing. Therefore, this project is aimed at investigating the feasibility of using a nanoparticle technology of NanoTrans for topical administration of a model drug diclofenac, for the management of choroidal neovascularization. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that is off patent, allowing its use in conjunction with proprietary NanoTrans nanoparticle technologies for product development. Further, diclofenac eye drops are currently approved for human use, especially for treating inflammation of the eye surface and the anterior eye segment, minimizing the regulatory hurdles in the development nanoparticle eye drops of diclofenac. Diclofenac inhibits cyclooxygenase (COX) enzymes and hence inflammatory mediators including vascular endothelial growth factor (VEGF), a key growth factor underlying the pathology of choroidal neovascularization. However, currently available eye drop formulations of diclofenac do not deliver the drug to the back of the eye in adequate amounts for the drug to be effective in treating choroidal neovascularization. The purpose of this study is to test the hypothesis that nanoparticles surface functionalized with a permeability enhancing ligand can increase diclofenac delivery from an eye drop to the back of the eye, resulting in improved efficacy in a laser induced choroid neovascularization model. Besides CNV treatment, the proposed diclofenac nanoparticles are of potential value in treating other inflammatory disorders of the back of the eye. The findings and technologies developed in this study can potentially be extrapolated to other therapeutic agents intended for treating disorders of the back of the eye. , ,
Public Health Relevance: Age related macular degeneration (AMD) is a disease of the back of the eye that can cause blindness. The available treatments require frequent injections into the eye, which is painful, inconvenient, and potentially damaging to the eye. The proposed project is aimed at the development of an eye drop dosage form based on nanoparticle technologies of NanoTrans for treating AMD. Use of nanoparticle technologies of NanoTrans are expected to improve drug delivery to the back of the from an eye drop. Such an approach avoids the pitfalls associated with invasive drug administrations. The proposed technologies are likely to benefit various drugs intended for treating diseases of the back of the eye.
Thesaurus Terms: (5z,8z,11z,14z)-Icosa-5,8,11,14-Tetraenoate,Hydrogen-Donor[{..}]oxygen Oxidoreductase;2-Deoxy-2-((Methylnitrosoamino)Carbonyl)Amino-D-Glucose;2-Deoxy-2-(3-Methyl-3-Nitrosoureido)-D-Glucopyranose;2-Deoxy-2-[[(Methylnitrosamino)-Carbonyl]amino]-D-Glucopyranose;21+ Years Old;5 Year Old;Adult;Age;Age Related Macular Degeneration;Angiogenic Factor;Anterior Eye Segment;Anterior Eyeball Segment Structure;Anti-Inflammatories;Anti-Inflammatory Agents;Anti-Inflammatory;Antiinflammatories;Antiinflammatory Agents;Arachidonic Acid Cyclooxygenase;Area;Back;Benzeneacetic Acid, 2-((2,6-Dichlorophenyl)Amino)-;Benzenesulfonamide, 4-[5-(4-Methylphenyl)-3-(Trifluoromethyl)-1h-Pyrazol-1-Yl]-;Blindness;Blood Vessels;Body Tissues;Cox;Cox Inhibitor;Cox2 Inhibitor;Categories;Cell Nucleus;Choroid;Choroidal Neovascularization;Ciliary Body;Common Rat Strains;Consensus;Coxibs;Cyclo-Oxygenase;Cyclooxygenase;Cyclooxygenase 2 Inhibitors;Cyclooxygenase Inhibitors;Development;Diabetes Mellitus;Dichlofenal;Diclofenac;Dicrofenac;Dinoprostone;Disadvantaged;Disease;Disorder;Dorsum;Dosage Forms;Dose;Drug Administration, Topical;Drug Delivery;Drug Delivery Systems;Drug Exposure;Drug Formulations;Drug Targeting;Drug Targetings;Drugs;Electromagnetic, Laser;Encapsulated;Endophthalmitis;Enzymes;Eye;Eye Drops;Eyeball;Eyedrops;Factor, Angiogenesis;Fatty Acid Cyclo-Oxygenase;Formulation;Formulations, Drug;Gfac;Genes;Growth Agents;Growth Factor;Growth Factor Inhibition;Growth Factors, Proteins;Growth Substances;Hbgf;Heumann Brand Of Celecoxib;Human;Human, Adult;Human, General;Hydroperoxide Cyclase;Hypoxia Inducible Factor;Inflm;Incidence;Inflammation;Inflammation Mediators;Inflammatory;Inhibitors, Cyclo-Oxygenase;Injection Of Therapeutic Agent;Injections;International;Iris;Iris (Eye);Lasers;Lead;Legal Patent;Length Of Life;Ligands;Longevity;Mack Brand Of Celecoxib;Maculopathy, Age-Related;Mammals, Rats;Man (Taxonomy);Man, Modern;Medication;Methods And Techniques;Methods, Other;Modeling;Morphology;Neovascularization, Choroid;Nucleus;Ophthalmia;Pge2;Pge2 Alpha;Pge2alpha;Pgh Synthase;Pgh2 Synthetase;Pain;Painful;Parke Davis Brand Of Celecoxib;Patents;Pathologic;Pathology;Pathway Interactions;Patients;Pb Element;Permeability;Pfizer Brand Of Celecoxib;Pharmaceutic Preparations;Pharmaceutical Preparations;Pharmacia Spain Brand Of Celecoxib;Pharmacia Brand Of Celecoxib;Phase;Photochemotherapy;Photodynamic Therapy;Play;Population;Posterior Eye Segment;Posterior Eyeball Segment Structure;Procedures;Process;Prosta-5,13-Dien-1-Oic Acid, 11,15-Dihydroxy-9-Oxo-, (5z,11alpha,13e,15s)-;Prostaglandin Cyclo-Oxygenase;Prostaglandin Cyclooxygenase;Prostaglandin E2;Prostaglandin E2 Alpha;Prostaglandin E2alpha;Prostaglandin Endoperoxide Synthase Inhibitors;Prostaglandin Endoperoxide Synthetase;Prostaglandin G-H Synthase;Prostaglandin H Synthase;Prostaglandin H2 Synthetase;Prostaglandin Synthase;Prostaglandin Synthase Inhibitors;Prostaglandin Synthesis Antagonists;Prostaglandin Synthetase;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Prostanoids;Radiation, Laser;Rat;Rattus;Recurrence;Recurrent;Reporting;Retina;Retinal;Retinal Detachment;Risk Factors;Rodent Model;Role;Route;Sttr;Stz;Safety;Searle Brand Of Celecoxib;Small Business Technology Transfer Research;Streptozocin;Streptozotocin;Surface;System;System, Loinc Axis 4;Techniques;Technology;Testing;Therapeutic;Therapeutic Agents;Tissues;Topical Application;Treatment Efficacy;Vegfs;Vascular Endothelial Growth Factor A;Vascular Endothelial Growth Factors;Vasculotropin;Vegf;Voltaren;Zanosar;Adult Human (21+);Angiogenesis;Base;Celebrex;Celecoxib;Clinical Applicability;Clinical Application;Conjunctiva;Design;Designing;Diabetes;Disease/Disorder;Drug Clearance;Drug/Agent;Five Year Old;Heavy Metal Pb;Heavy Metal Lead;Improved;Laser Photocoagulation;Life Span;Lifespan;Nano Particle;Nanoparticle;Neoplasm/Cancer Photoradiation Therapy;Pathway;Product Development;Public Health Relevance;Retina Detachment;Senile Macular Disease;Social Role;Therapeutic Efficacy;Therapeutically Effective;Topical Administration;Topical Drug Application;Topically Applied;Transcription Factor;Vascular;Zeta Potential
