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|Title:||Novel Antipsychotic Drug Carriers: The Development of Nanoparticle and Microgel Drug Carriers for Antipsychotic Delivery in the Treatment of Schizophrenia|
|Authors:||Piazza, Justin E.|
|Advisor:||Mishra, Ram K.|
Selvaganapathy, Ravi P.
|Keywords:||nanoparticle;microgel;antipsychotic;allosteric modulator;PAOPA;Amino Acids, Peptides, and Proteins;Biochemistry;Biomaterials;Cell Biology;Medicinal Chemistry and Pharmaceutics;Molecular and Cellular Neuroscience;Molecular Biology;Nanomedicine;Nervous System Diseases;Pharmaceutics and Drug Design;Polymer Science;Psychiatric and Mental Health;Toxicology;Amino Acids, Peptides, and Proteins|
|Abstract:||<p>Lectin-functionalized, Poly [oligo(ethylene glycol) methyl ether methacrylate] (<em>POEGMA</em>) loaded with 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) and poly(ethylene glycol)–block-poly(D,L-lactic-co-glycolic acid) (PEG-PLGA) nanoparticles loaded with haloperidol were prepared with narrow size distributions and sizes < 135 nm. The microgels and nanoparticles exhibited high <em>Solanum tuberosum </em>lectin (STL) conjugation efficiencies, encapsulation efficiencies, and drug loading capacities. The <em>in vitro</em> release of PAOPA and haloperidol was slow in physiological conditions over 96 hours, demonstrating minimal drug leakage and the potential for efficient drug transport to the targeted brain tissue. POAPA, POEGMA and the STL-functionalized POEGMA microgels were found to be non-toxic in both cell lines, indicating that they would not be toxic when administered intranasally or when they reach the brain. The nasal epithelial cell uptake of rhodamine-labelled microgels was higher in cells when the STL-functionalization was present. All haloperidol-loaded nanoparticle formulations were found to be highly effective at inducing catalepsy, while intranasal administration of STL-functionalized nanoparticles using the intranasal spray device increased the brain tissue haloperidol concentrations by 2-3.5 fold compared to STL-functionalized particles administered intranasally with a pipette. For the first time, brain tissue concentrations of rhodamine-labelled microgels confirmed that microgels are capable of passing the blood-brain barrier and that this uptake is size dependent. These formulations demonstrate promise in the reduction of the drug dose necessary to produce a therapeutic effect with antipsychotic drugs for the treatment of schizophrenia using a non-invasive route of administration.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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