Stabilization of a model formalinized protein antigen encapsulated in poly(lactide- co -glycolide)-based microspheres
dc.contributor.author | Jiang, Wenlei | en_US |
dc.contributor.author | Schwendeman, Steven P. | en_US |
dc.date.accessioned | 2006-04-19T13:37:24Z | |
dc.date.available | 2006-04-19T13:37:24Z | |
dc.date.issued | 2001-10 | en_US |
dc.identifier.citation | Jiang, Wenlei; Schwendeman, Steven P. (2001)."Stabilization of a model formalinized protein antigen encapsulated in poly(lactide- co -glycolide)-based microspheres." Journal of Pharmaceutical Sciences 90(10): 1558-1569. <http://hdl.handle.net/2027.42/34504> | en_US |
dc.identifier.issn | 0022-3549 | en_US |
dc.identifier.issn | 1520-6017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34504 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11745714&dopt=citation | en_US |
dc.description.abstract | A formaldehyde-mediated aggregation pathway (FMAP) has been shown to be primarily responsible for the solid-state aggregation of lyophilized formalinized protein antigens [e.g., tetanus toxoid (TT) and formalinized bovine serum albumin (f-BSA)] in the presence of moisture and physiological temperature. Coincorporation of the formaldehyde-interacting amino acid, histidine, strongly inhibits the FMAP. The purpose of this study was to test whether previous solid-state data are applicable toward the stabilization of formalinized antigens encapsulated in poly(lactide- co -glycolide) (PLGA)-based microspheres. Formaldehyde-treated bovine serum albumin (f-BSA) and BSA were selected as a model formalinized protein antigen and a nonformalinized control, respectively. As in the solid state, we found that the FMAP was dominant in the aggregation of f-BSA encapsulated in PLGA 50/50 microspheres, whereas the aggregation mechanism of encapsulated BSA was mostly converted from thiol–disulfide interchange to an acid-catalyzed noncovalent pathway. The lack of noncovalent aggregation in encapsulated f-BSA could be explained by its higher thermodynamic stability after formalinization, which inhibits protein unfolding. Targeting the FMAP, coencapsulation of histidine and trehalose successfully inhibited the aggregation of f-BSA in microspheres. By combining the use of an optimized oil-in-oil (o/o) encapsulation method, coencapsulation of histidine and trehalose, and use of low-acid-content poly( D , L -lactide) (PLA) and poly(ethylene glycol) (PEG) blends, a 2-month continuous release of f-BSA was achieved with the absence of aggregation. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1558–1569, 2001 | en_US |
dc.format.extent | 282879 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Inc. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | Stabilization of a model formalinized protein antigen encapsulated in poly(lactide- co -glycolide)-based microspheres | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan 48109-1065 ; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210 | en_US |
dc.contributor.affiliationum | Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan 48109-1065 ; Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan 48109-1065. Telephone: 734-615-6574; Fax: 734-615-6162 | en_US |
dc.identifier.pmid | 11745714 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34504/1/1106_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/jps.1106 | en_US |
dc.identifier.source | Journal of Pharmaceutical Sciences | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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