Linked Life Data

19886803

Source:http://linkedlifedata.com/resource/pubmed/id/19886803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-9-29
pubmed:abstractText
BACKGROUND AND AIMS: Antibodies to tumor necrosis factor alpha (TNF-?) have been successful in treating perianal fistulae in Crohn's disease, but current modes of delivery are limited. Microspheres are currently being assessed as scaffolds for tissue engineering and drug delivery devices. The aim of this study was to produce anti-TNF-? antibody-encapsulated microspheres using thermally induced phase separation (TIPS) and to characterize their behavior. METHODS: Anti-TNF-? antibody was encapsulated into the microspheres (100 mg infliximab/g poly[lactide-co-glycolide] w/w) using a novel technique combining a vibration encapsulator unit with a TIPS process, using either lyophilized particulate antibody or an aqueous solution of antibody. Microspheres were incubated in phosphate-buffered saline for collection of supernatant and assessment of degradation. The amount and biological activity of the encapsulated antibody released from the microspheres was assessed by enzyme-linked immunosorbent assay and its ability to neutralize recombinant human (rh)TNF-? in vitro with a cytotoxicity assay. An in vitro wound scratch assay was used to assess the effect of released antibody on fibroblast migration. Ultrastructural characteristics of the different microspheres were characterized by scanning electron microscopy. Results: Highly porous microspheres released anti-TNF-? antibody under zero-order kinetics and inhibited the cytotoxic activity of rhTNF-?, producing a significant increase in cell viability compared with cells treated with rhTNF-? alone. This effect was most pronounced with microspheres fabricated by blending lyophilized particulate anti-TNF-? antibody into the polymer solution, which also significantly reduced the release of lactate dehydrogenase. Summary and Conclusions: Anti-TNF-? antibody encapsulated into highly porous microspheres was released in a controlled manner and exhibited biological activity against TNF-?. The technique used to produce TIPS microspheres is rapid and provides high encapsulation efficiency. This technique could also be applied to other therapeutic peptides where rapid fabrication and high yields are required.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1937-3392
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
855-64
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Anti-tumor necrosis factor-alpha-loaded microspheres as a prospective novel treatment for Crohn's disease fistulae.
pubmed:affiliation
Centre for Gastroenterology and Nutrition, Windeyer Institute, University College London, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't