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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
5R41MH098521-02
Application #
8545220
Study Section
Special Emphasis Panel (ZRG1-IMST-M (13))
Program Officer
Grabb, Margaret C
Project Start
2012-09-13
Project End
2014-08-28
Budget Start
2013-09-01
Budget End
2014-08-28
Support Year
2
Fiscal Year
2013
Total Cost
$97,615
Indirect Cost
Name
Lnkchemsolutions
Department
Type
DUNS #
131068186
City
Lincoln
State
NE
Country
United States
Zip Code
68521