Dextran retention in the rat brain following release from a polymer implant
Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran).
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
1992 |
|---|---|
| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Biotechnology progress - 8(1992), 6 vom: 01. Nov., Seite 527-32 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dang, W [VerfasserIn] |
|---|
| Themen: |
Dextrans |
|---|
| Anmerkungen: |
Date Completed 01.02.1993 Date Revised 23.11.2016 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM012623512 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM012623512 | ||
| 003 | DE-627 | ||
| 005 | 20231221053116.0 | ||
| 007 | tu | ||
| 008 | 231221s1992 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0042.xml |
| 035 | |a (DE-627)NLM012623512 | ||
| 035 | |a (NLM)1282018 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dang, W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dextran retention in the rat brain following release from a polymer implant |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 01.02.1993 | ||
| 500 | |a Date Revised 23.11.2016 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Dextrans |2 NLM | |
| 650 | 7 | |a Drug Implants |2 NLM | |
| 650 | 7 | |a Polymers |2 NLM | |
| 650 | 7 | |a fluorescein isothiocyanate dextran |2 NLM | |
| 650 | 7 | |a Fluorescein-5-isothiocyanate |2 NLM | |
| 650 | 7 | |a I223NX31W9 |2 NLM | |
| 700 | 1 | |a Saltzman, W M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biotechnology progress |d 1985 |g 8(1992), 6 vom: 01. Nov., Seite 527-32 |w (DE-627)NLM012623482 |x 1520-6033 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:1992 |g number:6 |g day:01 |g month:11 |g pages:527-32 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 1992 |e 6 |b 01 |c 11 |h 527-32 | ||