Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems : protein release and protein stability issues. / van de Weert, Marco; van Steenbergen, Marinus J; Cleland, Jeffrey L; Heller, Jorge; Hennink, Wim E; Crommelin, Daan J A.

In: Journal of Pharmaceutical Sciences, Vol. 91, No. 4, 04.2002, p. 1065-74.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

van de Weert, M, van Steenbergen, MJ, Cleland, JL, Heller, J, Hennink, WE & Crommelin, DJA 2002, 'Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues', Journal of Pharmaceutical Sciences, vol. 91, no. 4, pp. 1065-74.

APA

van de Weert, M., van Steenbergen, M. J., Cleland, J. L., Heller, J., Hennink, W. E., & Crommelin, D. J. A. (2002). Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues. Journal of Pharmaceutical Sciences, 91(4), 1065-74.

Vancouver

van de Weert M, van Steenbergen MJ, Cleland JL, Heller J, Hennink WE, Crommelin DJA. Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues. Journal of Pharmaceutical Sciences. 2002 Apr;91(4):1065-74.

Author

van de Weert, Marco ; van Steenbergen, Marinus J ; Cleland, Jeffrey L ; Heller, Jorge ; Hennink, Wim E ; Crommelin, Daan J A. / Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems : protein release and protein stability issues. In: Journal of Pharmaceutical Sciences. 2002 ; Vol. 91, No. 4. pp. 1065-74.

Bibtex

@article{e1879e84e6644349b08cc487b0e44434,
title = "Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues",
abstract = "Semisolid, self-catalyzed poly(ortho ester)s (POEs), are investigated as potential sustained-release systems for proteins. In this study, some factors influencing protein release kinetics and protein instability were evaluated. As model proteins, lysozyme, alpha-lactalbumin, bovine serum albumin, and vascular endothelial growth factor, which were lyophilized from various buffer solutions in the absence and presence of lyoprotectants, were used. For all protein formulations, the release kinetics followed the visually observed polymer dissolution profile. In the absence of any buffers in the protein formulation, the release was continuous. Formulations containing a buffer below pH 7 accelerated POE degradation, resulting in faster protein release. In contrast, a strong buffer capacity at pH 7 reduced the POE degradation and resulted in a biphasic release pattern. Moreover, proteins with a high isoelectric point (pI > 7) appeared to catalyze the POE degradation, and the effect of the buffer strength and pH was much smaller than for proteins with low pI (<7). In the absence of lyoprotectants, all proteins tested showed an increasing fraction of covalent protein aggregates during the release. Protein formulations containing a lyoprotectant, such as sucrose or trehalose, did not show a significantly increased aggregation, whereas there was a minor influence of the large solid loadings on the release kinetics. In conclusion, this semisolid, self-catalyzed POE showed good promise as a sustained-release matrix for bioactive proteins.",
author = "{van de Weert}, Marco and {van Steenbergen}, {Marinus J} and Cleland, {Jeffrey L} and Jorge Heller and Hennink, {Wim E} and Crommelin, {Daan J A}",
note = "Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1065-1074, 2002",
year = "2002",
month = "4",
language = "English",
volume = "91",
pages = "1065--74",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems

T2 - protein release and protein stability issues

AU - van de Weert, Marco

AU - van Steenbergen, Marinus J

AU - Cleland, Jeffrey L

AU - Heller, Jorge

AU - Hennink, Wim E

AU - Crommelin, Daan J A

N1 - Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1065-1074, 2002

PY - 2002/4

Y1 - 2002/4

N2 - Semisolid, self-catalyzed poly(ortho ester)s (POEs), are investigated as potential sustained-release systems for proteins. In this study, some factors influencing protein release kinetics and protein instability were evaluated. As model proteins, lysozyme, alpha-lactalbumin, bovine serum albumin, and vascular endothelial growth factor, which were lyophilized from various buffer solutions in the absence and presence of lyoprotectants, were used. For all protein formulations, the release kinetics followed the visually observed polymer dissolution profile. In the absence of any buffers in the protein formulation, the release was continuous. Formulations containing a buffer below pH 7 accelerated POE degradation, resulting in faster protein release. In contrast, a strong buffer capacity at pH 7 reduced the POE degradation and resulted in a biphasic release pattern. Moreover, proteins with a high isoelectric point (pI > 7) appeared to catalyze the POE degradation, and the effect of the buffer strength and pH was much smaller than for proteins with low pI (<7). In the absence of lyoprotectants, all proteins tested showed an increasing fraction of covalent protein aggregates during the release. Protein formulations containing a lyoprotectant, such as sucrose or trehalose, did not show a significantly increased aggregation, whereas there was a minor influence of the large solid loadings on the release kinetics. In conclusion, this semisolid, self-catalyzed POE showed good promise as a sustained-release matrix for bioactive proteins.

AB - Semisolid, self-catalyzed poly(ortho ester)s (POEs), are investigated as potential sustained-release systems for proteins. In this study, some factors influencing protein release kinetics and protein instability were evaluated. As model proteins, lysozyme, alpha-lactalbumin, bovine serum albumin, and vascular endothelial growth factor, which were lyophilized from various buffer solutions in the absence and presence of lyoprotectants, were used. For all protein formulations, the release kinetics followed the visually observed polymer dissolution profile. In the absence of any buffers in the protein formulation, the release was continuous. Formulations containing a buffer below pH 7 accelerated POE degradation, resulting in faster protein release. In contrast, a strong buffer capacity at pH 7 reduced the POE degradation and resulted in a biphasic release pattern. Moreover, proteins with a high isoelectric point (pI > 7) appeared to catalyze the POE degradation, and the effect of the buffer strength and pH was much smaller than for proteins with low pI (<7). In the absence of lyoprotectants, all proteins tested showed an increasing fraction of covalent protein aggregates during the release. Protein formulations containing a lyoprotectant, such as sucrose or trehalose, did not show a significantly increased aggregation, whereas there was a minor influence of the large solid loadings on the release kinetics. In conclusion, this semisolid, self-catalyzed POE showed good promise as a sustained-release matrix for bioactive proteins.

M3 - Journal article

C2 - 11948545

VL - 91

SP - 1065

EP - 1074

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 4

ER -

ID: 45184797