In vitro and in vivo release properties of brilliant blue and tumour necrosis factor-alpha (TNF-alpha) from poly(D,L-lactic-co-glycolic acid) multiphase microspheres
The dissolution properties of two model compounds, brilliant blue and tumour necrosis factor (TNF-alpha), from poly(D,L-lactic-co-glycolic acid) (PLGA) multiphase microspheres were investigated. In addition, the in vivo release of TNF-alpha from the microspheres, in mice, was studied. The microspheres were prepared by an anhydrous multiple emulsion solvent evaporation method. Multiphase microspheres containing brilliant blue exhibited a three phase release profile in vitro, and displayed a significantly lower level of dye released during the initial phase compared to conventional matrix-type microspheres. Slow release of the dye was observed during the second phase, which was followed by a disintegration of the polymer wall during the third phase of the release process. In vitro dissolution profiles of TNF-alpha were calculated by compensation for the simultaneous degradation of the protein in the dissolution medium. The initial burst release of TNF-alpha was significantly reduced with the multiphase microspheres. The three phase release profile, as seen with the dye, was not observed for the microspheres containing the TNF-alpha. The rate of release of the protein from the microspheres was determined in vivo by analysing the residual level of TNF-alpha remaining in the particles following intraperitoneal administration of the microspheres to mice. The release of the protein from the microspheres in vivo was significantly faster than predicted from the results of the in vitro studies. The absence of an initial burst release of TNF-alpha from the multiphase microspheres was reflected in a significant reduction in the plasma level of TNF-alpha when compared to the matrix-type microspheres and a solution of the protein. The controlled release property of the multiphase microspheres is expected to overcome the adverse reactions due to dose dumping that occurs following the local administration of TNF-alpha.
Medienart: |
Artikel |
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Erscheinungsjahr: |
1999 |
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Erschienen: |
1999 |
Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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Enthalten in: |
Journal of microencapsulation - 16(1999), 6 vom: 30. Nov., Seite 777-92 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Iwata, M [VerfasserIn] |
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Anmerkungen: |
Date Completed 24.01.2000 Date Revised 03.11.2019 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM105056022 |
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100 | 1 | |a Iwata, M |e verfasserin |4 aut | |
245 | 1 | 0 | |a In vitro and in vivo release properties of brilliant blue and tumour necrosis factor-alpha (TNF-alpha) from poly(D,L-lactic-co-glycolic acid) multiphase microspheres |
264 | 1 | |c 1999 | |
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500 | |a Date Completed 24.01.2000 | ||
500 | |a Date Revised 03.11.2019 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a The dissolution properties of two model compounds, brilliant blue and tumour necrosis factor (TNF-alpha), from poly(D,L-lactic-co-glycolic acid) (PLGA) multiphase microspheres were investigated. In addition, the in vivo release of TNF-alpha from the microspheres, in mice, was studied. The microspheres were prepared by an anhydrous multiple emulsion solvent evaporation method. Multiphase microspheres containing brilliant blue exhibited a three phase release profile in vitro, and displayed a significantly lower level of dye released during the initial phase compared to conventional matrix-type microspheres. Slow release of the dye was observed during the second phase, which was followed by a disintegration of the polymer wall during the third phase of the release process. In vitro dissolution profiles of TNF-alpha were calculated by compensation for the simultaneous degradation of the protein in the dissolution medium. The initial burst release of TNF-alpha was significantly reduced with the multiphase microspheres. The three phase release profile, as seen with the dye, was not observed for the microspheres containing the TNF-alpha. The rate of release of the protein from the microspheres was determined in vivo by analysing the residual level of TNF-alpha remaining in the particles following intraperitoneal administration of the microspheres to mice. The release of the protein from the microspheres in vivo was significantly faster than predicted from the results of the in vitro studies. The absence of an initial burst release of TNF-alpha from the multiphase microspheres was reflected in a significant reduction in the plasma level of TNF-alpha when compared to the matrix-type microspheres and a solution of the protein. The controlled release property of the multiphase microspheres is expected to overcome the adverse reactions due to dose dumping that occurs following the local administration of TNF-alpha | ||
650 | 4 | |a Comparative Study | |
650 | 4 | |a Journal Article | |
650 | 7 | |a Benzenesulfonates |2 NLM | |
650 | 7 | |a Polymers |2 NLM | |
650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
650 | 7 | |a Polylactic Acid-Polyglycolic Acid Copolymer |2 NLM | |
650 | 7 | |a 1SIA8062RS |2 NLM | |
650 | 7 | |a Polyglycolic Acid |2 NLM | |
650 | 7 | |a 26009-03-0 |2 NLM | |
650 | 7 | |a Lactic Acid |2 NLM | |
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650 | 7 | |a H3R47K3TBD |2 NLM | |
700 | 1 | |a Nakamura, Y |e verfasserin |4 aut | |
700 | 1 | |a McGinity, J W |e verfasserin |4 aut | |
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