SBIR-STTR Award

Otitis media (infection of the middle ear space) is one of the most common diseases of childhood. Myringotomy with tympanostomy tube (TT) insertion is the most common operation performed on children in the United States. Otorrhea is the most common complication following tube insertion and can occur in up to 17% of ears receiving TT and is often associated with active infection. Current treatments involve the administration of antibiotic or antibiotic/steroid drops twice a day for 14 days. Though this decreases the incidence of infection, there are issues with patient compliance and temporary conductive hearing loss in the children. An enhanced treatment option would improve treatment efficacy, increase patient compliance, and eliminate the temporary hearing loss. This Phase I SBIR proposal involves the fabrication of therapeutic treatments for otitis media associated with tympanostomy tubes in children. The specific aims of this proposal present a roadmap towards the early stage development of an extended release hydrogel to deliver steroids and antibiotics locally for 14 days. The aims of this proposal are threefold: First, the development of prototype extended release composition of the therapeutic formulation to incorporate the desired therapeutic dose and release duration. Second, the development of an injectable hydrogel containing these extended release drugs. Third, the activity of the release therapeutics will be analyzed utilizing cell culture analyses. This will yield a prototype formulation for further study The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, drug development and drug delivery for the successful development this product. O-Ray scientists have successfully developed therapeutic formulations that are currently being used in the clinic. This includes an intraocular sustained release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for periods of up to 3 years from a single implantation. Phase II of this project will involve the testng of stability and sterility of these formulations, and safety and pharmacokinetic animal studies sufficient to lead to an Investigational New Drug Exemption. The completion of this work will ultimately facilitate a collaboration with a corporate partner for the licensing of our developed product.

Thesaurus Terms:
Affect;Animal Model;Animals;Anti-Inflammatory;Anti-Inflammatory Agents;Antibiotics;Biological Assay;Cell Culture Techniques;Cells;Child;Childhood;Ciprofloxacin;Clinic;Clinical Trials;Collaborations;Compliance Behavior;Complication;Conductive Hearing Loss;Development;Dexamethasone;Disease;Dose;Drops;Drug Delivery Systems;Drug Development;Drug Formulations;Drug Kinetics;Ear Structure;Environment;Exhibits;Experience;Future;Gel;Goals;Guidelines;Hearing Impairment;Hydrogels;Implant;Implantation;Improved;In Vitro Activity;In Vitro Assay;Incidence;Individual;Infection;Inflammation;Injectable;Injection Of Therapeutic Agent;Investigational Drugs;Lead;Licensing;Mediating;Methods;Middle Ear;Needles;Operation;Otitis Media;Otology;Otorrhea;Ototoxicity;Particle;Pharmaceutical Preparations;Phase;Phase 2 Study;Polymers;Preparation;Prevention;Product Development;Prototype;Public Health Relevance;Qualifying;Research Personnel;Risk;Safety;Scientist;Small Business Innovation Research Grant;Stability Testing;Staging;Sterility;Steroids;Suspension Substance;Suspensions;Testing;Therapeutic;Time;Treatment Efficacy;Tube;Tympanostomy;Tympanostomy Tube Insertions;United States;Viscosity;Work;

Otitis media (infection of the middle ear space) is one of the most common diseases of childhood. Myringotomy with tympanostomy tube (TT) insertion is the most common operation performed on children in the United States. Otorrhea is the most common complication following tube insertion and can occur in up to 17% of ears receiving TT and is often associated with active infection. Current treatments involve the administration of antibiotic or antibiotic/steroid drops twice a day for 14 days. Though this decreases the incidence of infection, there are issues with patient compliance and temporary conductive hearing loss in the children. An enhanced treatment option would improve treatment efficacy and increase patient compliance. This Phase II SBIR proposal involves the validation of manufacturing and safety of therapeutic treatments for otitis media associated with tympanostomy tubes in children. The specific aims of this proposal present a roadmap towards the development of an extended release hydrogel to deliver steroids and antibiotics locally for 14 days. The aims of this proposal are threefold: First, manufacturing of the components of the extended release hydrogel using FDA guidelines for GMP manufacturing for Phase 1 clinical trials will be done. Second, the sterility and stability of the components of the extended release hydrogel will be tested. Lastly, a well- controlled study assessing the safety of the extended release hydrogel and its components will be performed under Good Laboratory Practice conditions. The completion of this project will finish all preclinical studies required for the initiation of Phase I clinical studies. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, drug development and drug delivery for the successful development this product. O-Ray scientists have successfully developed therapeutic formulations that are currently being used in the clinic. This includes an intraocular sustained release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for periods of up to 3 years from a single implantation. The next stage of this project will involve the collaboration with a corporate partner for the licensing of our developed product and the initiation of clinical trials.

Public Health Relevance Statement:
Project Narrative Myringotomy with tympanostomy tube insertion is the most common operation performed on children in the United States and is accompanied by frequent complications of otorrhea, often containing active infection (otitis media). An enhancement over the current treatment option would improve treatment efficacy, increase patient compliance, and eliminate the temporary hearing loss. This Phase II SBIR proposal involves the validation of manufacture and safety of therapeutic treatments for otitis media associated with tympanostomy tubes in children.

NIH Spending Category:
Bioengineering; Infectious Diseases; Otitis Media; Patient Safety; Pediatric; Prevention

Project Terms:
Affect; Animal Model; Anti-inflammatory; Anti-Inflammatory Agents; Antibiotics; Cavia; Child; Childhood; Ciprofloxacin; Clinic; Clinical Research; Clinical Trials; Collaborations; Compliance behavior; Complication; Conductive hearing loss; Controlled Study; Development; Dexamethasone; Disease; Dose; Drops; Drug Delivery Systems; drug development; Ear; Effectiveness; Environment; experience; FDA approved; Formulation; Funding; Future; Goals; good laboratory practice; Guidelines; Hearing; hearing impairment; Histology; Hydrogels; Implant; implantation; improved; Incidence; Industry; Infection; Injectable; Injection of therapeutic agent; Investigational Drugs; Labyrinth; Licensing; Marketing; Medical Device; Methods; middle ear; Modeling; Monitor; operation; Otitis Media; Otology; Otorrhea; particle; Penetration; Performance; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Polymers; preclinical safety; preclinical study; Preparation; Prevention; Procedures; product development; Qualifying; Research Contracts; Research Personnel; Risk; Safety; safety study; Scientist; Small Business Innovation Research Grant; stability testing; Staging; Sterility; Sterilization; Steroids; success; Suspension substance; Suspensions; Testing; Therapeutic; Time; Toxic effect; Treatment Efficacy; Tube; Tympanostomy; Tympanostomy Tube Insertions; United States; Validation; Work