Microspheres for protein delivery prepared from amphiphilic multiblock copolymers: 1. influence of preparation techniques on particle characteristics and protein delivery

J.M. Bezemer, R. Radersma, D.W. Grijpma, P.J. Dijkstra, C.A. van Blitterswijk, J. Feijen

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4% poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.
Original languageEnglish
Pages (from-to)233-248
JournalJournal of controlled release
Volume67
Issue number2-3
DOIs
Publication statusPublished - 2000

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Microspheres
Muramidase
Emulsions
Water
Oils
Proteins
Methanol
Ethanol
Alcohols
Pyrrolidinones
Ethylene Glycol
Polymers

Keywords

  • Block copolymer
  • Protein
  • Microsphere
  • Controlled release

Cite this

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title = "Microspheres for protein delivery prepared from amphiphilic multiblock copolymers: 1. influence of preparation techniques on particle characteristics and protein delivery",
abstract = "The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4{\%} poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.",
keywords = "Block copolymer, Protein, Microsphere, Controlled release",
author = "J.M. Bezemer and R. Radersma and D.W. Grijpma and P.J. Dijkstra and {van Blitterswijk}, C.A. and J. Feijen",
year = "2000",
doi = "10.1016/S0168-3659(00)00213-3",
language = "English",
volume = "67",
pages = "233--248",
journal = "Journal of controlled release",
issn = "0168-3659",
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Microspheres for protein delivery prepared from amphiphilic multiblock copolymers : 1. influence of preparation techniques on particle characteristics and protein delivery. / Bezemer, J.M.; Radersma, R.; Grijpma, D.W.; Dijkstra, P.J.; van Blitterswijk, C.A.; Feijen, J.

In: Journal of controlled release, Vol. 67, No. 2-3, 2000, p. 233-248.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Microspheres for protein delivery prepared from amphiphilic multiblock copolymers

T2 - 1. influence of preparation techniques on particle characteristics and protein delivery

AU - Bezemer, J.M.

AU - Radersma, R.

AU - Grijpma, D.W.

AU - Dijkstra, P.J.

AU - van Blitterswijk, C.A.

AU - Feijen, J.

PY - 2000

Y1 - 2000

N2 - The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4% poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.

AB - The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4% poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.

KW - Block copolymer

KW - Protein

KW - Microsphere

KW - Controlled release

U2 - 10.1016/S0168-3659(00)00213-3

DO - 10.1016/S0168-3659(00)00213-3

M3 - Article

VL - 67

SP - 233

EP - 248

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

IS - 2-3

ER -