The investigators propose to develop nanoparticulate biodegradable polymeric oral delivery systems for therapeutic agents representative of hydrophobic small molecules, proteins, and genes, and will study their uptake, as further described by their abstract: """"""""Our project focuses on the development of nanoparticle-based, oral delivery systems, composed of biodegradable polymers, used to efficiently encapsulate and increase the bioavailability and uptake of three representative therapeutic agents from the most active fields of current research: small hydrophobic molecules (taxol), proteins (insulin) and genes. """"""""Although much research has been performed with the first two systems, still there is a challenge to improve the oral bioavailability of these drugs. No product is commercially available on the market, particularly for the oral delivery of peptides and proteins. The last system is the most challenging one, since very little work has been done on oral delivery of genes. """"""""Our hypothesis is that if we succeed in enhancing uptake of drug-loaded nanoparticles, then we may be able to enhance the bioavailability of each of the potential drug candidates. For taxol and insulin, we will target an increase in systemic bioavailability, while for plasmids the nature of he enhancement may be either local or systemic.""""""""

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM055245-01A1
Application #
2396927
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Brown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Kawauchi, Shimako; Santos, Rosaysela; Kim, Joon et al. (2009) The role of foxg1 in the development of neural stem cells of the olfactory epithelium. Ann N Y Acad Sci 1170:21-7
Kawauchi, Shimako; Calof, Anne L; Santos, Rosaysela et al. (2009) Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-) mouse, a model of Cornelia de Lange Syndrome. PLoS Genet 5:e1000650
Sandor, M; Mehta, S; Harris, J et al. (2002) Transfection of HEK cells via DNA-loaded PLGA and P(FASA) nanospheres. J Drug Target 10:497-506
Sandor, Maryellen; Harris, Joshua; Mathiowitz, Edith (2002) A novel polyethylene depot device for the study of PLGA and P(FASA) microspheres in vitro and in vivo. Biomaterials 23:4413-23
Sandor, Maryellen; Riechel, Alex; Kaplan, Ian et al. (2002) Effect of lecithin and MgCO3 as additives on the enzymatic activity of carbonic anhydrase encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres. Biochim Biophys Acta 1570:63-74
Sandor, M; Enscore, D; Weston, P et al. (2001) Effect of protein molecular weight on release from micron-sized PLGA microspheres. J Control Release 76:297-311
Egilmez, N K; Jong, Y S; Hess, S D et al. (2000) Cytokines delivered by biodegradable microspheres promote effective suppression of human tumors by human peripheral blood lymphocytes in the SCID-Winn model. J Immunother 23:190-5