title: Biodegradable poly(terephthalate-co-phosphate)s: synthesis, characterization and drug-release properties.
abstract: To develop biodegradable polymers with favorable physicochemical and biological properties, we have synthesized a series of poly(terephthalate-co-phosphate)s using a two-step poly-condensation. The diol 1,4-bis(2-hydroxyethyl) terephthalate was first reacted with ethylphosphorodichloridate (EOP), and then chain-extended with terephthaloyl chloride (TC). Incorporation of phosphate into the poly(ethylene terephthalate) backbone rendered the co-polymers soluble in chloroform and biodegradable, lowered the Tg, decreased the crystallinity and increased the hydrophilicity. With an EOP/TC molar feed ratio of 80: 20, the polymer exhibited good film-forming property, yielding at 86.6 +/- 1.6% elongation with an elastic modulus of 13.76 +/- 2.66 MPa. This polymer showed a favorable toxicity profile in vitro and good tissue biocompatibility in the muscular tissue of mice. In vitro the polymer lost 21% of mass in 21 days, but only 20% for up to 4 months in vivo. It showed no deterioration of properties after sterilization by gamma-irradiation at 2.5 Mrad on solid CO2. Release of FITC-BSA from the microspheres was diffusion-controlled and exceeded 80% completion in two days. Release of the hydrophobic cyclosporine-A from microspheres was however much more sustained and near zero-ordered, discharging 60% in 70 days. A limited structure-property relationship has been established for this co-polymer series. The co-polymers became more hydrolytically labile as the phosphate component (EOP) was increased and the side chains were switched from the ethoxy to the methoxy structure. Converting the methoxy group to a sodium salt further increased the degradation rate significantly. The chain rigidity as reflected in the Tg values of the co-polymers decreased according to the following diol structure in the backbone: ethylene glycol > 2-methylpropylene diol > 2,2-dimethylpropylene diol. The wide range of physicochemical properties obtainable from this co-polymer series should help the design of degradable biomaterials for specific biomedical applications.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 726 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
authors.forename: Irina
authors.initials: I
authors.lastname: Shipanova-Kadiyala
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Wenbin
authors.initials: W
authors.lastname: Dang
authors.forename: Angela
authors.initials: A
authors.lastname: Brown
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001673:Biodegradation, Environmental; D002460:Cell Line; D006801:Humans; D008863:Microspheres; D010755:Organophosphates / Q000737:chemistry*; D010795:Phthalic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D010755:Organophosphates; D010795:Phthalic Acids; D011108:Polymers; C110732:bis-(2-hydroxyethyl)terephthalate; D012710:Serum Albumin, Bovine; C011363:terephthalic acid; C059743:terephthaloyl chloride