A functionalized, injectable hydrogel for localized drug delivery with tunable thermosensitivity: synthesis and characterization of physical and toxicological properties.
Thermosensitive injectable hydrogels have been used for the delivery of pharmacological and cellular therapies in a variety of soft tissue applications. A promising class of synthetic, injectable hydrogels based upon oligo(ethylene glycol) methacrylate (OEGMA) monomers has been previously reported, but these polymers lack reactive groups for covalent attachment of therapeutic molecules. In this work, thermosensitive, amine-reactive and amine-functionalized polymers were developed by incorporation of methacrylic acid N-hydroxysuccinimide ester or 2-aminoethyl methacrylate into OEGMA-based polymers. A model therapeutic peptide, bivalirudin, was conjugated to the amine-reactive hydrogel to investigate effects on the polymer thermosensitivity and gelation properties. The ability to tune the thermosensitivity of the polymer in order to compensate for peptide hydrophilicity and maintain gelation capability below physiological temperature was demonstrated. Cell encapsulation studies using an H9 T-cell line (CD4+) were conducted to evaluate feasibility of the hydrogel as a carrier for cellular therapies. Although this class of polymers is generally considered to be non-toxic, it was found that concentrations required for gelation were incompatible with cell survival. Investigation into the cause of cytotoxicity revealed that a hydrolysis byproduct, diethylene glycol monomethyl ether, is likely a contributing factor. While modifications to structure or composition will be required to enable viable cell encapsulation, the functionalized injectable hydrogel has the potential for controlled delivery of a wide range of drugs.
['Elias|Paul Z|PZ|', 'Liu|Gary W|GW|', 'Wei|Hua|H|', 'Jensen|Michael C|MC|', 'Horner|Philip J|PJ|', 'Pun|Suzie H|SH|']
D000588:Amines D000818:Animals D000925:Anticoagulants D002460:Cell Line D002470:Cell Survival D064987:Cell- and Tissue-Based Therapy D003300:Copper D004337:Drug Carriers D004339:Drug Compounding D016503:Drug Delivery Systems D006461:Hemolysis D006629:Hirudins D006358:Hot Temperature D006801:Humans D020100:Hydrogels D066298:In Vitro Techniques D008689:Methacrylates D051379:Mice D041681:NIH 3T3 Cells D010446:Peptide Fragments D011092:Polyethylene Glycols D011109:Polymethacrylic Acids D011994:Recombinant Proteins
Injectable hydrogel Drug delivery Peptide Cell therapy Immunotherapy Spinal cord injury