Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current protein replacement therapies for hemophilia B, a genetic bleeding disorder caused by a deficiency in coagulation factor IX, rely on IV injections and infusions. Oral delivery of factor IX is a desirable needle-free option, especially for prophylaxis. We have developed a biodegradable, pH-responsive hydrogel microcarrier system based on the poly(methacrylic acid)-grafted-poly(ethylene glycol) [P(MAA-g-EG)]. Incorporation of an enzymatically degradable peptide crosslinking agent allows for site-specific degradation by trypsin in the small intestine. P(MAA-g-EG) polymer was synthesized by UV polymerization, and then subsequently crosslinked with peptide crosslinking agent using EDC-NHS chemistry. Physical characterization included FTIR for determining the composition of the peptide crosslinked polymer and SEM for microparticle morphology. The pH-responsive swelling and enzyme-specific degradation were confirmed by bright-field microscopy and the corresponding kinetics were determined by turbidimetric measurements. Evaluating the drug delivery application of this degradable system, factor IX release studies showed site-specific release, and in vitro transport studies resulted in improved factor IX absorption. Incorporation of the degradable crosslinking agent significantly improved the delivery potential as compared to previously reported non-degradable drug delivery systems. Using this degradable P(MAA-g-EG) system as a delivery vehicle for factor IX can possibly lead to an orally administered prophylactic treatment for hemophilia B patients.
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PMID:Biodegradable hydrophilic carriers for the oral delivery of hematological factor IX for hemophilia B treatment. 2786 65


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