This program plans to develop a drug delivery system that provides maximum drug exposure and suppress residual human immunodeficiency virus (HIV)* in the brain and tissues of central nervous system (CNS). The advent of highly active antiretroviral combination drug therapies (HAART) has reduced plasma virus concentration to undetectable level and has extended life-expectancy in HIV+ subjects. However, residual virus in the CNS tissues, experiencing limited drug exposure is related to neuroAIDS disease progression. In collaboration with University of Washington, Impel NeuroPharma has developed a novel technology that will overcome limited CNS drug access thereby allowing a maximum drug exposure and viral suppression. Instead of depositing drugs to nasal cells (achieved with traditional nasal delivery devices), this technology deposits drugs in olfactory cells and provides direct access to the brain and CNS, thereby improving the efficiency of CNS delivery. The proposed UW collaboration will allow Impel to further optimize and develop this device for delivery of anti-HIV drugs into the brain and CNS and evaluating it in appropriate animal models. We envisioned that this product will be used to suppress virus in the CNS as an adjunct to the current oral HARRT, which are effective for suppressing HIV in blood. [*Abbreviation list is enclosed at the end of references]
Public Health Relevance: The proposed University of Washington collaborative research will allow Impel NeuroPharma, Inc to further optimize and develop this device for delivery of anti-HIV drugs into the brain and CNS and evaluating it in appropriate preclinical models. We envisioned that this product will be used to suppress virus in the CNS as an adjunct to the current oral HARRT, which are effective for suppressing HIV in blood.
Public Health Relevance Statement: The proposed University of Washington collaborative research will allow Impel NeuroPharma, Inc to further optimize and develop this device for delivery of anti-HIV drugs into the brain and CNS and evaluating it in appropriate preclinical models. We envisioned that this product will be used to suppress virus in the CNS as an adjunct to the current oral HARRT, which are effective for suppressing HIV in blood.
Project Terms: 9-(2-phosphonomethoxypropyl)adenine; 9-(2-phosphonylmethoxypropyl)adenine; 9-PMPA; AIDS Virus; AIDS neuropathy; Abbreviations; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Aerosols; Animal Model; Animal Models and Related Studies; Anti-Retroviral Agents; Antiretroviral Agents; Architecture; Awards and Prizes; Blood; Blood Plasma; Body Tissues; Brain; Businesses; CNS agent; Cells; Central Nervous System; Central Nervous System Agents; Central Nervous System Drugs; Chronic Phase; Collaborations; Combination Drug Therapy; Common Rat Strains; Contrast Agent; Contrast Drugs; Contrast Media; Deposit; Deposition; Device Designs; Devices; Disease Progression; Dose; Drug Delivery; Drug Delivery Systems; Drug Exposure; Drug Formulations; Drug Kinetics; Drug Targeting; Drug Targetings; Drug or chemical Tissue Distribution; Drugs; Encephalon; Encephalons; Engineering / Architecture; Epithelium, Olfactory; Exposure to; Formulation; Formulations, Drug; Frequencies (time pattern); Frequency; Gadolinium DTPA; Gadolinium Diethylenetriaminepenta-acetic Acid; Gadopentetic Acid; Gd-DTPA; Goals; HIV; HTLV-III; Human; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human, General; Image; Individual; Investigators; Kaletra; LAV-HTLV-III; Life Expectancy; Lopinavir; Lopinavir/Ritonavir; Lymphadenopathy-Associated Virus; Magnetism; Mammals, Primates; Mammals, Rats; Man (Taxonomy); Man, Modern; Medication; Modeling; N-(4-(((2,6-dimethylphenoxy)acetyl)amino)-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl)tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2H)-pydrimidineacetamide; Nasal; Nasal cavity; Nervous System, Brain; Nervous System, CNS; Neuraxis; Neurologic; Neurological; Nomograms; Nose; Nose, Nasal Passages; Olfactory Epithelium; Oral; PMPA; Performance; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacokinetics; Plasma; Polychemotherapy; Pre-Clinical Model; Preclinical Models; Primates; Programs (PT); Programs [Publication Type]; Radiopaque Media; Rat; Rattus; Research; Research Design; Research Personnel; Researchers; Residual; Residual state; Respiratory System, Nose, Nasal Passages; Reticuloendothelial System, Blood; Reticuloendothelial System, Serum, Plasma; SCHED; Schedule; Serum, Plasma; Study Type; System; System, LOINC Axis 4; Technology; Tenofovir; Therapeutic; Tissue Distribution; Tissues; Universities; Validation; Viral; Viral Diseases; Virus; Virus Diseases; Virus-HIV; Viruses, General; Washington; anti-retroviral; antiretroviral; base; brain tissue; centrally acting drug; chemical property; combination pharmacotherapy; design; designing; drug/agent; experience; imaging; improved; magnetic; model organism; neuroAIDS; new technology; novel; pinacolyl methylphosphonic acid; prevent; preventing; programs; prototype; public health relevance; response; site targeted delivery; study design; targeted delivery; therapeutic evaluation; viral infection; virus infection
