A5074541667- Nanoparticle-Based Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Extracellular vesicles in disease
- Barrier Structure and Function Studies
- Protein purification and stability
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Blood properties and coagulation
- RNA Interference and Gene Delivery
- Complement system in diseases
- Blood Coagulation and Thrombosis Mechanisms
- Acute Ischemic Stroke Management
- Biosimilars and Bioanalytical Methods
- Drug Solubulity and Delivery Systems
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Advanced Drug Delivery Systems
- Mechanical Circulatory Support Devices
- Blood groups and transfusion
- HER2/EGFR in Cancer Research
- Veterinary Oncology Research
Temple University
2023-2025
Translational Therapeutics (United States)
2017-2024
University of Pennsylvania
2017-2024
Temple College
2024
Target (United States)
2017-2022
Philadelphia University
2020
California University of Pennsylvania
2020
University at Buffalo, State University of New York
2014-2018
Boston University
1961-1965
Significance Drug delivery to the brain is a challenging and elusive goal. Conjugating with ligands of target molecules including transferrin receptor modestly enhances cerebral accumulation drugs drug carriers. We found that conjugating VCAM-1 provides order(s) magnitude higher nanocarriers, especially in inflamed brain. targeted nanocarriers loaded messenger RNA encoding endothelial glycoprotein thrombomodulin cause expression transgene lumen vasculature. This alleviates pathological...
Abstract Molecular targeting of nanoparticle drug carriers promises maximized therapeutic impact to sites disease or injury with minimized systemic effects. Precise demands addressing subcellular features. Caveolae, invaginations in cell membranes implicated transcytosis and inflammatory signaling, are appealing targets. Caveolar geometry has been reported impose a ≈50 nm size cutoff on nanocarrier access plasmalemma vesicle associated protein (PLVAP), marker found caveolae the lungs. The...
Ex vivo-loaded white blood cells (WBC) can transfer cargo to pathological foci in the central nervous system (CNS). Here we tested affinity ligand driven vivo loading of WBC order bypass need for ex manipulation. We used a mouse model acute brain inflammation caused by local injection tumor necrosis factor alpha (TNF-α). intravenously injected nanoparticles targeted intercellular adhesion molecule 1 (anti-ICAM/NP). found that (A) at 2 h, >20% anti-ICAM/NP were localized lungs; (B) lungs >90%...
Diseases of the pulmonary alveolus, such as fibrosis, are leading causes morbidity and mortality, but exceedingly few drugs developed for them. A major reason this gap is that after inhalation, quickly whisked away from alveoli due to their high perfusion. To solve problem, mechanisms by which nano‐scale drug carriers dramatically improve lung pharmacokinetics using an inhalable liposome formulation containing nintedanib, antifibrotic studied. Direct instillation liposomes in murine...
Complement opsonization is among the biggest challenges facing nanomedicine. Nearly instantly after injection into blood, nanoparticles are opsonized by complement protein C3, leading to clearance phagocytes, fouling of targeting moieties, and release anaphylatoxins. While surface polymers such as poly(ethylene glycol) (PEG) partially decrease opsonization, most still suffer from extensive especially when linked moieties. To ameliorate deleterious effects complement, two mammals' natural...
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics pharmacodynamics of a protein cargo. Affinity targeting Factor IX (FIX) RBC membrane is promising approach improve (pro)enzyme's pharmacokinetics. For targeting, purified human FIX was conjugated anti-mouse glycophorin A monoclonal antibody Ter119. The goal this study characterize activity FIX-Ter119 conjugate efficacy its loading on RBCs, well investigate biodistribution,...
The immune checkpoint inhibitor (ICI) ipilimumab has revolutionized the treatment of patients with different cancer histologies, including melanoma, renal cell carcinoma, and non-small lung carcinoma. However, only a subset shows dramatic clinical responses to treatment. Despite intense biomarker discovery efforts linked trials using CTLA4 blockade, no single prognostic correlate emerged as valid predictor outcome. Client-owned, competent, pet dogs develop spontaneous tumors that exhibit...
Engineering drug delivery systems for prolonged pharmacokinetics (PK) has been an ongoing pursuit nearly 50 years. The gold standard PK enhancement is the coating of nanoparticles with polymers, namely polyethylene glycol (PEGylation), which applied in several clinically used products. In present work, we utilize longest circulating and most abundant component blood─the erythrocyte─to improve behavior liposomes. Antibody-mediated coupling liposomes to erythrocytes was tested vitro identify a...
The use of single-domain antibody fragments, or nanobodies, has gained popularity in recent years as an alternative to traditional monoclonal antibody-based approaches. Relatively little is known, however, about the utility nanobodies targeting agents for delivery therapeutic cargoes, particularly vascular epitopes setting acute inflammatory conditions. We used a nanobody (VCAMelid) directed against mouse cell adhesion molecule 1 (VCAM-1) and techniques site-specific radiolabeling...