The long-term goal of this proposal is to develop novel nanoparticles, """"""""platelet-mimicking nanoparticles,"""""""" as a drug carrier that can target and deliver a therapeutic agent to the injured vessel wall after cardiovascular interventions such as angioplasty. Our strategy is to mimic the binding of the glycoprotein Ib (GPIb) of platelets (a blood cell type) through either P-selectin expressed in damaged endothelial cells (ECs) or vWF deposited on injured subendothelium, which is critical for the initial interaction of circulating platelets onto the injured vessel wall under high shear conditions. The major advantage of using GPIb-nanoparticles for targeting drug delivery in our proposal, compared to current targeting strategies including anti-P-selectin antibodies, is that GPIb specially binds to both P- selectin expressed on damaged ECs and vWF deposited on injured subendothelium, thereby accumulating more nanoparticles as drug carriers to the injured wall site for effective drug delivery. To accomplish our goal, three specific aims are: (1) Develop drug (dexamethasone)-loaded biodegradable GPIb-nanoparticles using a standard double emulsion method. (2) Investigate the targeting activity and effectiveness of these nanoparticles in vitro using the parallel flow plate system, surfaces coated with P-selectin or vWF, and activated ECs. (3) Evaluate the efficacy of our novel platelet-mimicking nanoparticles in vivo using rat balloon injury models. The assessed parameters for these specific aims include the binding sites and stability of GPIb, changes in nanoparticle properties, the adhesion and uptake of GPIb-nanoparticles in activated endothelial cells under flow conditions as well as pharmacological activities of these nanoparticles in inflamed ECs and injured rat arteries. Cardiovascular interventions often injure the vessel wall, leading to the development of late pathological conditions such as inflammation and restenosis. The development of our novel platelet- mimicking nanoparticles is a unique strategy to rapidly target and deliver therapeutic agents to damaged ECs and subendothelium, despite the shear influence, for more effective therapies to treat these complications. ? ? ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Danthi, Narasimhan
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University of Texas Arlington
Biomedical Engineering
Schools of Engineering
United States
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Xu, Hao; Kona, Soujanya; Su, Lee-Chun et al. (2013) Multi-ligand poly(L-lactic-co-glycolic acid) nanoparticles inhibit activation of endothelial cells. J Cardiovasc Transl Res 6:570-8
Kona, Soujanya; Dong, Jing-Fei; Liu, Yaling et al. (2012) Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system. Int J Pharm 423:516-24
Kona, Soujanya; Specht, Danyel; Rahimi, Maham et al. (2012) Targeted biodegradable nanoparticles for drug delivery to smooth muscle cells. J Nanosci Nanotechnol 12:236-44
Wu, Yangzhe; Yu, Tian; Gilbertson, Timothy A et al. (2012) Biophysical assessment of single cell cytotoxicity: diesel exhaust particle-treated human aortic endothelial cells. PLoS One 7:e36885
Koppolu, Bhanuprasanth; Rahimi, Maham; Nattama, Sivaniarvindpriya et al. (2010) Development of multiple-layer polymeric particles for targeted and controlled drug delivery. Nanomedicine 6:355-61
Lin, Arthur; Sabnis, Abhimanyu; Kona, Soujanya et al. (2010) Shear-regulated uptake of nanoparticles by endothelial cells and development of endothelial-targeting nanoparticles. J Biomed Mater Res A 93:833-42
Rahimi, Maham; Wadajkar, Aniket; Subramanian, Khaushik et al. (2010) In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery. Nanomedicine 6:672-80
Rahimi, Maham; Yousef, Monet; Cheng, Yuhang et al. (2009) Formulation and characterization of a covalently coated magnetic nanogel. J Nanosci Nanotechnol 9:4128-34
Sabnis, Abhimanyu; Wadajkar, Aniket S; Aswath, Pranesh et al. (2009) Factorial analyses of photopolymerizable thermoresponsive composite hydrogels for protein delivery. Nanomedicine 5:305-15
Sabnis, Abhimanyu; Rahimi, Maham; Chapman, Christopher et al. (2009) Cytocompatibility studies of an in situ photopolymerized thermoresponsive hydrogel nanoparticle system using human aortic smooth muscle cells. J Biomed Mater Res A 91:52-9

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