| Localized delivery of proteins in the brain: can transport be customized? | |
| | |
MedLine Citation:
|
PMID: 9563066 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Certain central nervous system (CNS) diseases are characterized by the degeneration of specific cell populations. One strategy for treating neurodegenerative diseases is long-term, controlled delivery of proteins such as epidermal growth factor (EGF) and nerve growth factor (NGF). Since proteins permeate through brain capillaries very slowly, local administration using polymeric implants, continuous infusion pumps, or transplanted, protein-secreting cells may be required to achieve therapeutic concentrations in the tissue. The efficiency of local distribution, and hence effectiveness of local therapy, depends on the rate of protein migration through tissue. The rate of dispersion of molecules in a quiescent, isotropic medium can be characterized by the molecular diffusion coefficient, D, which can be measured by techniques such as quantitative autoradiography, iontophoresis, and fluorescence photobleaching recovery (FPR). These methods are reviewed, with an emphasis on their application to measurement of D for proteins in the brain. Biophysical techniques yield quantitative descriptions of local protein distribution and may enable discrimination of mechanisms of protein transport in the brain. This capability suggests a new paradigm for design of protein therapies, in which proteins and delivery systems are collectively customized to provide sustained protein availability over predetermined volumes of tissue. |
| | |
Authors:
|
M F Haller; W M Saltzman |
Related Documents
:
|
1384556 - Subpopulations of neurons in the guinea-pig inferior mesenteric ganglia distinguished b... 823816 - Nutritional studies in the pregnant rhesus monkey--the effect of protein-calorie or pro... 2822856 - S-100 protein in clonal astroglioma cells is released by adrenocorticotropic hormone an... 6202856 - Immunohistochemistry of central nervous system tumors. its contributions to neurosurgic... 21295546 - Evidence for involvement of the c-terminal domain in the dimerization of the copy repre... 475516 - The effects of cortisol on protein metabolism and on transfer ribonucleic acid methylas... |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
|
Title: Pharmaceutical research Volume: 15 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1998 Mar |
Date Detail:
|
Created Date: 1998-07-29 Completed Date: 1998-07-29 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 377-85 Citation Subset: IM |
Affiliation:
|
School of Chemical Engineering, Cornell University, Ithaca, New York 14853, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Autoradiography Blood-Brain Barrier / drug effects Brain / blood supply, drug effects, metabolism* Diffusion Drug Delivery Systems Drug Implants Epidermal Growth Factor / metabolism, therapeutic use* Fluorescence Humans Iontophoresis Models, Theoretical Nerve Growth Factors / metabolism, therapeutic use* Neurodegenerative Diseases / drug therapy*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
CA52857/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Drug Implants; 0/Nerve Growth Factors; 62229-50-9/Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Drug exsorption from blood into the gastrointestinal tract.
Next Document: Advances and challenges in the prevention and treatment of Alzheimer's disease.