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BSA degradation under acidic conditions: A model for protein instability during release from PLGA delivery systems

dc.contributor.authorEstey, Tiaen_US
dc.contributor.authorKang, Jichaoen_US
dc.contributor.authorSchwendeman, Steven P.en_US
dc.contributor.authorCarpenter, John F.en_US
dc.date.accessioned2007-07-11T18:14:27Z
dc.date.available2007-07-11T18:14:27Z
dc.date.issued2006-07en_US
dc.identifier.citationEstey, Tia; Kang, Jichao; Schwendeman, Steven P.; Carpenter, John F. (2006). "BSA degradation under acidic conditions: A model for protein instability during release from PLGA delivery systems." Journal of Pharmaceutical Sciences 95(7): 1626-1639. <http://hdl.handle.net/2027.42/55225>en_US
dc.identifier.issn0022-3549en_US
dc.identifier.issn1520-6017en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/55225
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16729268&dopt=citationen_US
dc.description.abstractAcidification of the internal poly(lactide- co -glycolide) (PLGA) microenvironment is considered one of the major protein stresses during controlled release from such delivery systems. A model protein, bovine serum albumin (BSA), was incubated at 37°C for 28 days to simulate the environment within the aqueous pores of PLGA during the release phase and to determine how acidic microclimate conditions affect BSA stability. Size-exclusion high performance liquid chromatography (SE-HPLC), SDS–PAGE, and infrared spectroscopy were used to monitor BSA degradation. BSA was most stable at pH 7, but rapidly degraded via aggregation and hydrolysis at pH 2. These simulated degradation products were nearly identical to that of unreleased BSA found entrapped within PLGA 50/50 millicylinders. At pH 2, changes in BSA conformation detected by various spectroscopic techniques were consistent with acid denaturation of the protein. By contrast, at pH 5 and above, damage to BSA was insufficient to explain the instability of the protein in the polymer. Thus, these data confirm the hypothesis that acid-induced unfolding is the basis of BSA aggregation in PLGA and the acidic microclimate within PLGA is indeed a dominant stress for encapsulated BSA. To increase the stability of proteins within PLGA systems, formulations must protect against potentially extreme acidification such that native structure is maintained. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1626–1639, 2006en_US
dc.format.extent248001 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherChemistryen_US
dc.subject.otherFood Science, Agricultural, Medicinal and Pharmaceutical Chemistryen_US
dc.titleBSA degradation under acidic conditions: A model for protein instability during release from PLGA delivery systemsen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelPharmacy and Pharmacologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.contributor.affiliationotherDepartment of Pharmaceutical Sciences, School of Pharmacy, Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center, Denver, Colorado 80262en_US
dc.contributor.affiliationotherDepartment of Formulation Development, Neose Technologies, Inc., 102 Witmer Road, Horsham, Pennsylvania 19044en_US
dc.contributor.affiliationotherDepartment of Pharmaceutical Sciences, School of Pharmacy, Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center, Denver, Colorado 80262 ; Department of Pharmaceutical Sciences, School of Pharmacy, Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center, Denver, Colorado 80262. Telephone: 303-315-6073; Fax: 303-315-0274en_US
dc.identifier.pmid16729268en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/55225/1/20625_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/jps.20625en_US
dc.identifier.sourceJournal of Pharmaceutical Sciencesen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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