The goal of the proposed project is to develop a biocompatible ultrafine particle-based vector system for the intranasal delivery of clozapine for the pharmacological therapy of treatment- resistant schizophrenic disorders and their associated suicidal behavior. The rationale behind the use of intranasal clozapine is grounded on the observation of clozapine's extensive first- pass metabolism associated with buccal intake, clozapine's extensive binding to plasma proteins, its short elimination half-life, the absence of significantly active metabolites, and the potentially serious side effects brought about by the high oral doses required for therapeutic benefit. The LNK Chemsolutions LLC/University of Chicago team will use a series of particle design tools, in vivo, ex vivo and in vitro methods to develop the seminal Phase-I level research. Electrohydrodynamic methods will be used to design particles with well-defined sizes and drug payloads, using three different polymers. In vitro drug release examinations will be complemented by muco-adhesive tests, and ex vivo (swine nasal membrane) drug permeation studies. These will guide in vivo (mouse model) studies aimed at elucidating particle and drug transport.
Public Health Relevance: In this SBIR Phase I grant application, LNK Chemsolutions LLC and the University of Chicago researchers are partnering to develop an intranasal drug delivery platform for one anti-psychotic drug. In vitro and in vivo studies will be performed to investigate the potential of the proposed approach.
Public Health Relevance Statement: In this SBIR Phase I grant application, LNK Chemsolutions LLC and the University of Chicago researchers are partnering to develop an intranasal drug delivery platform for one anti-psychotic drug. In vitro and in vivo studies will be performed to investigate the potential of the proposed approach.
NIH Spending Category: Bioengineering; Brain Disorders; Mental Health; Nanotechnology; Schizophrenia
Project Terms: Adhesions; Adhesives; Adverse effects; Animals; Antipsychotic Agents; Applications Grants; base; Binding (Molecular Function); Biocompatible; Biodegradation; Blood; Brain; Bypass; Chicago; Clozapine; Complement; controlled release; cytotoxicity test; design; Development; Dose; drug clearance; Drug Delivery Systems; Drug Transport; Evaluation Studies; Family suidae; Frequencies (time pattern); Goals; Half-Life; Image; In Vitro; in vivo; Intake; Intranasal Administration; Liver; Lung; Membrane; Metabolism; Methods; Mind; Modality; Modeling; mouse model; nanofabrication; nanoparticle; Nose; Oral; particle; Particle Size; Pharmaceutical Preparations; Phase; Plasma Proteins; Polymers; Postdoctoral Fellow; Production; Research; Research Personnel; Resistance; Saline; Schizophrenia; Seminal; Series; Small Business Innovation Research Grant; Staging; suicidal behavior; Suspension substance; Suspensions; System; Technology; Testing; Therapeutic; tool; ultrafine particle; Universities; vector
