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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2001-8-22
pubmed:abstractText
The in vivo release characteristics of protein-loaded biodegradable microspheres were examined in normal rats and severe combined immunodeficiency disease (SCID) mice. Bovine-derived superoxide dismutase (bSOD), encapsulated into microspheres comprised of poly(D,L-lactic-co-glycolic acid) and poly(D,L-lactic acid), was used as a model protein. Three types of bSOD-loaded microspheres with different release profiles were subcutaneously administered to normal rats. Anti-bSOD antibodies were first detected at day 9 after the administration of these microspheres, which was independent of their release profiles in vitro. A typical formulation with a sigmoidal release profile was subcutaneously administered to SCID mice. No immunoreaction was observed. The plasma bSOD concentration-time profile, determined by an enzyme-linked immunosorbent assay, well reflected the in vitro release profile of the formulation. The disappearance profile of active bSOD from the administration site also partly corresponded to both profiles. However, the relative bioavailability calculated with a profile on the subcutaneous injection of bSOD solution was 40.7%. These results indicated possible instability of bSOD released gradually at the administration site. The results of the present study using SCID mice would be suitable for discussing the in vitro-in vivo correlation of protein release from microspheres, and useful for designing long-term release formulations of protein drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0168-3659
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Evaluation of in vivo release characteristics of protein-loaded biodegradable microspheres in rats and severe combined immunodeficiency disease mice.
pubmed:affiliation
DDS Research Department, Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89 Kashima, Yodogawa-ku, 532-8505, Osaka, Japan. t-morita@tanabe.co.jp
pubmed:publicationType
Journal Article