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Principal Investigator: Rebecca Long Heise
Organization: VIRGINIA COMMONWEALTH UNIVERSITY
Fiscal Year: 2019
Award: $181,005
Funding agency: National Heart Lung and Blood Institute
Acute Respiratory Distress Syndrome (ARDS) is diagnosed in 150,000 patients per year in the United States.
These types of lung injury may be caused by severe infection, inhaling dangerous substances, or trauma.
ARDS has a high impact on mortality with approximately half of all people diagnosed dying as a result of the
injury. No effective treatments exist for ARDS, and ventilator support is necessary for the patient to recover.
One reason there are no effective treatments is that pulmonary drug delivery is an area with many challenges
that is in need of novel approaches. The lungs have an aggressive innate and adaptive immune response in
combination with their complex structure, which makes delivering therapeutics difficult. In order to overcome
challenges in pulmonary drug delivery, nanoparticles may be utilized as delivery vehicles. Current nanoparticle
approaches such as lipid or polymer-based strategies may be rendered ineffective in the lung through
hydrolysis or may have dangerous degradation products. By using naturally-derived extracellular matrix (ECM)
proteins for the delivery vehicle, we can achieve an increase therapeutic effect. ECM-based nanoparticles
increase therapeutic effect through better cell attachment and regulating the immune response. Additionally,
ECM degradation has been shown to be antibacterial, and scaffolds made from these materials have been
accepted clinically for repair and reconstruction of other tissues. We hypothesize that engineered ECM
nanoparticles will be antibacterial and pro-regenerative to damaged lung tissue, enhancing the effects of
delivered therapeutics to treat ARDS. This hypothesis will be tested through two specific aims. In Aim 1 we will
quantify the antibiotic and pro-regenerative benefits of ECM nanoparticles delivered in vitro to primary lung
epithelium, neutrophils, and macrophages. In Aim 2 we will assess the delivery and regenerative potential of
ECM nanoparticles in an in vivo mouse model of lung injury. The ECM nanoparticles formed through
electrospray will provide a novel platform for drug delivery of biologics to the distal lung for improved treatment
options for ARDS and other lung diseases in the future.
Terms: <ARDS><Acute Lung Injury><Acute Pulmonary Injury><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Anti-Bacterial Agents><Anti-Inflammatories><Anti-Inflammatory Agents><Antibacterial Agents><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Antiinflammatories><Antiinflammatory Agents><Area><Bacterial Pneumonia><Biocompatible Materials><Biological><Biomaterials><Biomedical Engineering><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood capillaries><Body Tissues><Caliber><Cell Attachment><Cell Growth in Number><Cell Locomotion><Cell Migration><Cell Movement><Cell Multiplication><Cell Proliferation><Cell-Extracellular Matrix><Cell-Matrix Adhesions><Cell-Matrix Junction><Cellular Migration><Cellular Motility><Cellular Proliferation><Circulatory Collapse><Clinical><Cold-Insoluble Globulins><Collagen><Complex><Da Nang Lung><Dangerousness><Data><Deposit><Deposition><Diagnosis><Diameter><Diffuse><Disease><Disorder><Distal><Dosage Forms><Dose><Drug Carriers><Drug Delivery><Drug Delivery Systems><Drug Therapy><Drugs><ECM><Endothelial Cells><Engineering><Epithelium><Epithelium Part><Exhibits><Extracellular Matrix><Extracellular Matrix Degradation><Extracellular Matrix Proteins><Extravasation><FN1><Fibronectin 1><Fibronectins><Formulation><Future><Gastric Contents Aspirations><Glycosaminoglycans><Growth Agents><Growth Factor><Growth Substances><Hydrolysis><Hypoxemia><Immune response><Immunological response><In Vitro><Infection><Inflammatory><Inflammatory Response><Inhalation><Inhalators><Inhaler><Inhaling><Injury><LETS Proteins><Large External Transformation-Sensitive Protein><Leakage><Lipids><Lipopolysaccharides><Lung><Lung Compliance><Lung Parenchyma><Lung Respiratory System><Lung Tissue><Lung damage><Lung diseases><Lung infections><Marrow Neutrophil><Mechanical ventilation><Mechanics><Medication><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Motility><Mucopolysaccharides><Murine><Mus><Myocardium><Natural regeneration><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Opsonic Glycoprotein><Opsonic alpha(2)SB Glycoprotein><Oral><Patients><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacotherapy><Phenotype><Polymers><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Pre-Clinical Model><Preclinical Models><Production><Property><Proteins><Proteins Growth Factors><Proteoglycan><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Edema><Pulmonary aspiration of gastric contents><Radiation><Reaction><Regeneration><Regenerative Medicine><Resistance><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Route><Safety><Sepsis><Shock><Shock Lung><Spillage><Stiff lung><Structure><Structure of parenchyma of lung><Tendon structure><Tendons><Testing><Therapeutic><Therapeutic Effect><Tidal Volume><Tissues><Trauma><United States><Urinary tract><Ventilator><Work><adaptive immune response><aerosolized><alpha 2-Surface Binding Glycoprotein><anti-bacterial><anti-microbial><antibacterial><antimicrobial><base><bio-engineered><bio-engineers><biocompatibility><bioengineering><biological material><biomaterial compatibility><blood infection><bloodstream infection><bone><capillary><cardiac muscle><cell motility><circulatory shock><cytokine><disease of the lung><disorder of the lung><drug treatment><drug/agent><effective therapy><effective treatment><fighting><heart muscle><host response><hypoxemic><immunoresponse><improved><in vivo><lung development><lung disorder><lung edema><lung injury><lung repair><macrophage><mechanical><mechanical respiratory assist><mortality><mouse model><murine model><nano particle><nano particle delivery><nano-sized particle><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanosized particle><neutrophil><new approaches><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel strategies><novel strategy><novel therapeutics><novel therapy><oxidation><prevent><preventing><pulmonary><pulmonary infections><reconstruction><regenerate><regenerate new tissue><regenerating damaged tissue><regenerative><repair><repaired><resistant><respiratory><respiratory airway volume><scaffold><scaffolding><symptom treatment><symptomatic treatment><tissue regeneration><treat symptom><treatment strategy><wet lung>