Abstract

This is a grant renewal for studies on formulations of high molecular weight (MW less than 1000 Daltons) drugs, such as polypeptides. In this proposal, we intend to carry out studies towards understanding (and ultimately rationally improving) the stability of solid peptides and proteins within polymeric delivery systems. Specifically, we propose to examine the relationship between protein solid-state stability and 1) protein structure; and 2) Tg the glass transition temperature; then 3) examine the physical-chemical properties within polymers; and finally 4) apply the knowledge gained from above studies together towards examining stability of proteins loaded within polymeric matrices. We will use a number of model proteins with the goal of developing, for the first time, comprehensive guidelines for predicting and enhancing the stability of proteins under pharmaceutically relevant conditions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026698-19
Application #
2734410
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1979-07-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
19
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Schroeder, Avi; Goldberg, Michael S; Kastrup, Christian et al. (2012) Remotely activated protein-producing nanoparticles. Nano Lett 12:2685-9
Devitt, Gerard; Thomas, Mini; Klibanov, Alexander M et al. (2007) Optimized protocol for the large scale production of HIV pseudovirions by transient transfection of HEK293T cells with linear fully deacylated polyethylenimine. J Virol Methods 146:298-304
Thomas, Mini; Lu, James J; Zhang, Chengcheng et al. (2007) Identification of novel superior polycationic vectors for gene delivery by high-throughput synthesis and screening of a combinatorial library. Pharm Res 24:1564-71
Sharma, Vikas K; Klibanov, Alexander M (2007) Moisture-induced aggregation of lyophilized DNA and its prevention. Pharm Res 24:168-75
Berry, David; Lynn, David M; Berry, Eric et al. (2006) Heparin localization and fine structure regulate Burkitt's lymphoma growth. Biochem Biophys Res Commun 348:850-6
Thomas, Mini; Ge, Qing; Lu, James J et al. (2005) Cross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo. Pharm Res 22:373-80
Sharma, Vikas K; Thomas, Mini; Klibanov, Alexander M (2005) Mechanistic studies on aggregation of polyethylenimine-DNA complexes and its prevention. Biotechnol Bioeng 90:614-20
Colombo, Gaia; Padera, Robert; Langer, Robert et al. (2005) Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone. J Biomed Mater Res A 75:458-64
Haining, W Nicholas; Anderson, Daniel G; Little, Steven R et al. (2004) pH-triggered microparticles for peptide vaccination. J Immunol 173:2578-85
Klibanov, Alexander M; Schefiliti, Jennifer A (2004) On the relationship between conformation and stability in solid pharmaceutical protein formulations. Biotechnol Lett 26:1103-6

Showing the most recent 10 out of 90 publications