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The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres

Duncan, G. and Jess, T. and Mohamed, F. and Price, N. and Kelly, S. and Van Der Walle, C.F. (2005) The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres. Journal of Controlled Release, 110. pp. 34-48. ISSN 0168-3659

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Abstract

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for α-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a β-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.

Item type: Article
ID code: 10610
Keywords: poly(lactide-co-glycolide) microspheres; , circular dichroism, burst release, protein conformation; , Pharmacy and materia medica, Pharmaceutical Science
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Unknown Department
Faculty of Science > Institute of Photonics
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 24 Jun 2011 12:15
    Last modified: 04 Sep 2014 19:42
    URI: http://strathprints.strath.ac.uk/id/eprint/10610

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