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

Erscheinungsjahr:

1999

Erschienen:

1999

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Journal of microencapsulation - 16(1999), 6 vom: 30. Nov., Seite 777-92

Sprache:

Englisch

Beteiligte Personen:

Iwata, M [VerfasserIn]
Nakamura, Y [VerfasserIn]
McGinity, J W [VerfasserIn]

Themen:

1SIA8062RS
26009-03-0
33X04XA5AT
Benzenesulfonates
Brilliant blue
Comparative Study
H3R47K3TBD
Journal Article
Lactic Acid
Polyglycolic Acid
Polylactic Acid-Polyglycolic Acid Copolymer
Polymers
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 24.01.2000

Date Revised 03.11.2019

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM105056022