SBIR-STTR Award

The proposal seeks to initiate the development of a tetraethyl orthosilicate-based thixotropic antibiotic delivery systems for the treatment of otitis externa and prevention of malignant otitis externa. This study will set the foundation for the development of point-of-care, single application thixotropic drug delivery platform technologies for otic therapeutics.

Public Health Relevance Statement:
PROJECT SUMMARY Outer ear infections (otitis externa or OE) affect an estimated 10% of people in their lifetime, with associated healthcare costs amounting to over $500 million per year. The pathology is mostly treatable in the general population with topical antibiotics regimes, and can be supplemented in severe cases with systemic counterparts. However, incorrect application or non-compliance with the administration schedule of antibiotics leads to infection persistence, recurrence and potentially, the development of antibiotic resistant bacterial strains. In diabetic or elderly patients, the infection can be life threatening as it can progress into necrotizing or malignant otitis externa (MOE), with severe health consequences. In recent years, the incidence rate of MOE has seen a significant increase and has been associated with antibiotic resistant bacterial strains. There is, therefore, a critical need to develop safe and effective therapies for the treatment of OE and the prevention of MOE. With this proposal, we seek to initiate the development of an ototopical antibiotic delivery system that is liquid when shaken and can be deployed easily though a syringe or drop dispenser, yet that gels rapidly in place once the shear stress is removed. Such a delivery system would have the benefits of simple and effective topical application, would eliminate the risk of antibiotic administration regime noncompliance, and would enable the delivery in situ of active components at effective concentrations. We have already demonstrated that in in vitro assays tetraethyl orthosilicate thixotropic hydrogels, when loaded with an antibiotic, are fully inhibiting the growth of P. aeruginosa and S. aureus, the two bacterial strains prevalently associated with OE and MOE. We will test the biocompatibility of thixogels in standardized irritability and corrosion assays and investigate their ability to deliver a panel of standard antibiotics targeting both drug susceptible and drug resistant P. aeruginosa and S. aureus strains. These studies will set the foundation of Phase II, well-informed safety and effectiveness in vivo studies in animal models.

Project Terms:
Acute; Address; Affect; Aminoglycosides; Animal Model; Anti-Bacterial Agents; Antibiotics; Bacterial Antibiotic Resistance; Bacterial Infections; base; Biological Assay; biomaterial compatibility; Carbapenems; Ciprofloxacin; Classification; Clinical; clinical application; Collaborations; Constitution; Corrosion; cost; Data; Dependence; Development; diabetic patient; Disease; Doctor of Philosophy; Dose; Drops; Drug Delivery Systems; Drug resistant Pseudomonas aeruginosa; Ear; ear infection; effective therapy; Effectiveness; Epithelial; Etiology; External auditory canal; Formulation; Foundations; Funding; Gel; General Population; Goals; Growth; Health; Health Care Costs; Histologic; human model; Hydrogels; Imipenem; Immunocompromised Host; In Situ; in vitro Assay; in vivo; Incidence; Infection; insight; Kinetics; Labyrinth; Lactams; Left; Life; Liquid substance; Longevity; Malignant - descriptor; Medical Device; Methods; middle ear; Montana; multidisciplinary; Mupirocin; Mycoses; non-compliance; Nose; Ointments; older patient; Otitis Externa; pathogen; Pathology; Patients; Pharmaceutical Preparations; Phase; point of care; Postoperative Period; Prevention; product development; Production; Property; Protocols documentation; Pseudomonas aeruginosa; Recording of previous events; Recurrence; Reporting; Request for Proposals; Research; Resistance; Risk; Safety; Schedule; screening; shear stress; Site; Skin; skin irritation; Specific qualifier value; Standardization; Staphylococcus aureus; Staphylococcus aureus infection; Swelling; Syringes; System; Technology; Temperature; Testing; Therapeutic; three-dimensional modeling; Tissues; Topical Antibiotic; Topical application; Translating; Treatment Efficacy; Tympanic membrane; United States; Universities; Utah; Vancomycin; Viral; Virus Diseases; Work

The proposal seeks to initiate the development of a tetraethyl orthosilicate-based thixotropic antibiotic delivery systems for the treatment of otitis externa and prevention of malignant otitis externa. This study will set the foundation for the development of point-of-care, single application thixotropic drug delivery platform technologies for otic therapeutics.

Public Health Relevance Statement:
PROJECT SUMMARY Outer ear infections (otitis externa or OE) affect an estimated 10% of people in their lifetime, with associated healthcare costs amounting to over $500 million per year. The pathology is mostly treatable in the general population with topical antibiotics regimes, and can be supplemented in severe cases with systemic counterparts. However, incorrect application or non-compliance with the administration schedule of antibiotics leads to infection persistence, recurrence and potentially, the development of antibiotic resistant bacterial strains. In diabetic or elderly patients, the infection can be life threatening as it can progress into necrotizing or malignant otitis externa (MOE), with severe health consequences. In recent years, the incidence rate of MOE has seen a significant increase and has been associated with antibiotic resistant bacterial strains. There is, therefore, a critical need to develop safe and effective therapies for the treatment of OE and the prevention of MOE. With this proposal, we seek to initiate the development of an ototopical antibiotic delivery system that is liquid when shaken and can be deployed easily though a syringe or drop dispenser, yet that gels rapidly in place once the shear stress is removed. Such a delivery system would have the benefits of simple and effective topical application, would eliminate the risk of antibiotic administration regime noncompliance, and would enable the delivery in situ of active components at effective concentrations. We have already demonstrated that in in vitro assays tetraethyl orthosilicate thixotropic hydrogels, when loaded with an antibiotic, are fully inhibiting the growth of P. aeruginosa and S. aureus, the two bacterial strains prevalently associated with OE and MOE. We will test the biocompatibility of thixogels in standardized irritability and corrosion assays and investigate their ability to deliver a panel of standard antibiotics targeting both drug susceptible and drug resistant P. aeruginosa and S. aureus strains. These studies will set the foundation of Phase II, well-informed safety and effectiveness in vivo studies in animal models.

NIH Spending Category:
Antimicrobial Resistance; Bioengineering; Emerging Infectious Diseases; Infectious Diseases; Prevention

Project Terms:
Acute; Address; Affect; Aminoglycosides; Animal Model; Anti-Bacterial Agents; Antibiotics; Bacterial Antibiotic Resistance; Bacterial Infections; base; Biological Assay; biomaterial compatibility; Carbapenems; Ciprofloxacin; Classification; Clinical; clinical application; Collaborations; Constitution; Corrosion; cost; Data; Dependence; Development; diabetic patient; Disease; Doctor of Philosophy; Dose; Drops; Drug Delivery Systems; Drug resistant Pseudomonas aeruginosa; Ear; ear infection; effective therapy; Effectiveness; Epithelial; Etiology; External auditory canal; Formulation; Foundations; Funding; Gel; General Population; Goals; Growth; Health; Health Care Costs; Histologic; human model; Hydrogels; Imipenem; Immunocompromised Host; In Situ; in vitro Assay; in vivo; Incidence; Infection; insight; Kinetics; Labyrinth; Lactams; Left; Life; Liquid substance; Longevity; Malignant - descriptor; Medical Device; Methods; middle ear; Montana; multidisciplinary; Mupirocin; Mycoses; non-compliance; Nose; Ointments; older patient; Otitis Externa; pathogen; Pathology; Patients; Pharmaceutical Preparations; Phase; point of care; Postoperative Period; Prevention; product development; Production; Property; Protocols documentation; Pseudomonas aeruginosa; Recording of previous events; Recurrence; Reporting; Request for Proposals; Research; Resistance; Risk; Safety; Schedule; screening; shear stress; Site; Skin; skin irritation; Specific qualifier value; Standardization; Staphylococcus aureus; Staphylococcus aureus infection; Swelling; Syringes; System; Technology; Temperature; Testing; Therapeutic; three-dimensional modeling; Tissues; Topical Antibiotic; Topical application; Translating; Treatment Efficacy; Tympanic membrane; United States; Universities; Utah; Vancomycin; Viral; Virus Diseases; Work