title: Biodegradable hydrophilic carriers for the oral delivery of hematological factor IX for hemophilia B treatment.
abstract: 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.
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Sarena D
authors.initials: SD
authors.lastname: Horava
authors.affiliation: Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX, USA; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Moy
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX, USA; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX, USA; Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA. Electronic address: peppas@che.utexas.edu.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Peppas
mesh_terms: D000284:Administration, Oral; D063566:Biodegradable Plastics / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005164:Factor IX / Q000008:administration & dosage* / Q000737:chemistry*; D019073:HT29 Cells; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry
chemical_list: D063566:Biodegradable Plastics; D004337:Drug Carriers; D005079:Excipients; D010455:Peptides; D011108:Polymers; D011109:Polymethacrylic Acids; C099679:poly(methacrylic acid-ethylene glycol); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005164:Factor IX
keywords: Biodegradable polymer; Coagulation factor IX; Drug delivery; Hydrogels