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Lyophilization of protein-loaded polyelectrolyte microcapsules

Marie-Luce De Temmerman (UGent) , Joanna Rejman (UGent) , Johan Grooten (UGent) , Thomas De Beer (UGent) , Chris Vervaet (UGent) , Jo Demeester (UGent) and Stefaan De Smedt (UGent)
(2011) PHARMACEUTICAL RESEARCH. 28(7). p.1765-1773
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Organization
Abstract
Purpose To evaluate if lyophilization can be used to obtain a dry formulation of polyelectrolyte microcapsules, which have emerged as a new class of microparticles for the encapsulation and delivery of biomacromolecules. Methods Microcapsules composed of dextran sulfate and poly-L-arginine were obtained by coating CaCO(3) microparticles by means of the layer-by-layer technique. Microcapsules were lyophilized using different stabilizers; intactness was checked by CLSM and SEM. Horseradish peroxidase was encapsulated as model enzyme and retained activity after freeze-drying was determined using a fluorescence assay. Ovalbumin was encapsulated as model antigen; immunogenicity after lyophilization was evaluated in vitro by a T-cell proliferation assay and in vivo by measuring the antibody titer in mice. Results The results clearly demonstrate the necessity of using polyols in the formulation to prevent rupture of the microcapsules and to preserve the activity of encapsulated enzymes. Lyophilized microcapsules appeared as a promising adjuvant for antigen delivery, as both in vitro as in vivo assays showed higher immune activation compared to free antigen. Conclusions Lyophilization is a promising strategy towards improved stability of protein-loaded microcapsules.
Keywords
PHARMACEUTICALS, CAPSULES, MICROPARTICLES, drug delivery, encapsulation, layer-by-layer, lyophilization, microcapsules, MECHANICAL-PROPERTIES, MULTILAYER MICROCAPSULES, SUSTAINED-RELEASE, HOLLOW SPHERES, DRUG-RELEASE, ENCAPSULATION, PARTICLES

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Chicago
De Temmerman, Marie-Luce, Joanna Rejman, Johan Grooten, Thomas De Beer, Chris Vervaet, Jo Demeester, and Stefaan De Smedt. 2011. “Lyophilization of Protein-loaded Polyelectrolyte Microcapsules.” Pharmaceutical Research 28 (7): 1765–1773.
APA
De Temmerman, M.-L., Rejman, J., Grooten, J., De Beer, T., Vervaet, C., Demeester, J., & De Smedt, S. (2011). Lyophilization of protein-loaded polyelectrolyte microcapsules. PHARMACEUTICAL RESEARCH, 28(7), 1765–1773.
Vancouver
1.
De Temmerman M-L, Rejman J, Grooten J, De Beer T, Vervaet C, Demeester J, et al. Lyophilization of protein-loaded polyelectrolyte microcapsules. PHARMACEUTICAL RESEARCH. 2011;28(7):1765–73.
MLA
De Temmerman, Marie-Luce, Joanna Rejman, Johan Grooten, et al. “Lyophilization of Protein-loaded Polyelectrolyte Microcapsules.” PHARMACEUTICAL RESEARCH 28.7 (2011): 1765–1773. Print.
@article{2029613,
  abstract     = {Purpose To evaluate if lyophilization can be used to obtain a dry formulation of polyelectrolyte microcapsules, which have emerged as a new class of microparticles for the encapsulation and delivery of biomacromolecules. 
Methods Microcapsules composed of dextran sulfate and poly-L-arginine were obtained by coating CaCO(3) microparticles by means of the layer-by-layer technique. Microcapsules were lyophilized using different stabilizers; intactness was checked by CLSM and SEM. Horseradish peroxidase was encapsulated as model enzyme and retained activity after freeze-drying was determined using a fluorescence assay. Ovalbumin was encapsulated as model antigen; immunogenicity after lyophilization was evaluated in vitro by a T-cell proliferation assay and in vivo by measuring the antibody titer in mice. 
Results The results clearly demonstrate the necessity of using polyols in the formulation to prevent rupture of the microcapsules and to preserve the activity of encapsulated enzymes. Lyophilized microcapsules appeared as a promising adjuvant for antigen delivery, as both in vitro as in vivo assays showed higher immune activation compared to free antigen. 
Conclusions Lyophilization is a promising strategy towards improved stability of protein-loaded microcapsules.},
  author       = {De Temmerman, Marie-Luce and Rejman, Joanna and Grooten, Johan and De Beer, Thomas and Vervaet, Chris and Demeester, Jo and De Smedt, Stefaan},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {PHARMACEUTICALS,CAPSULES,MICROPARTICLES,drug delivery,encapsulation,layer-by-layer,lyophilization,microcapsules,MECHANICAL-PROPERTIES,MULTILAYER MICROCAPSULES,SUSTAINED-RELEASE,HOLLOW SPHERES,DRUG-RELEASE,ENCAPSULATION,PARTICLES},
  language     = {eng},
  number       = {7},
  pages        = {1765--1773},
  title        = {Lyophilization of protein-loaded polyelectrolyte microcapsules},
  url          = {http://dx.doi.org/10.1007/s11095-011-0411-z},
  volume       = {28},
  year         = {2011},
}

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