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 polycondensation. 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 T g , 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 γ -irradiation at 2.5 Mrad on solid CO 2 . 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 T g 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.

In situ characterization of moisture sorption/desorption in thin polymer films using optical waveguide spectroscopy

“…The synthesis of P(BHET-EOP/TC, 80:20) was described in details before [6]. The ratio in the notation refers to the molar ratio of EOP to TC units in the polymer backbone.…”

“…Recently, a new polyphosphoester co-polymer, namely P(BHET-EOP/TC), was developed in order to obtain not only the typical biodegradable characteristics of polyphosphoester but also to have strong mechanical properties by incorporating phosphates into the poly(ethylene terephthalate) (PET) backbone [6]. In contrast to PET, the co-polymer is more amorphous.…”

“…The pentavalency of the phosphorus atom in the backbone allows for chemical linkage of other molecules to the polymer. With an EOP/TC ratio of 80:20, the co-polymer showed a favorable toxicity profile in vitro and good tissue biocompatibility [6]. It was suggested that this class of biodegradable co-polymers may find use in biomedical applications, such as drug delivery and tissue engineering.…”

Syntheses of amphiphilic biodegradable copolymers of poly(ethyl ethylene phosphate) and poly(3-hydroxybutyrate) for drug delivery

“…For example, Wang et al have synthesized polyphosphoester with β-aminoethoxy side chain for gene delivery [14] . In addition, PPE can be synthesized by well controlled ring-opening polymerization of cyclic phosphoester monomers [9,15,16] . In this study, we synthesized novel ABA triblock copolymers (PEEP-b-PHB-b-PEEP) through ring-opening polymerization of ethyl ethylene phosphate (EEP) using PHB-diol as macroinitiator.…”

Recent Progress in Polyphosphoesters: From Controlled Synthesis to Biomedical Applications

“…[68] FITC-labeled bovine serum albumin (FITC-BSA) was encapsulated in the microspheres of these copolymers, and the release of FITC-BSA exceeded 80% in two days which was diffusioncontrolled. However, the release of hydrophobic cyclosporine-A from the microspheres was much more sustained and near zero-ordered, discharging 60% over 70 d. [68] Nanoparticles can passively accumulate in solid tumor tissues and enhance the therapeutic efficiency through the enhanced permeability and retention effect (EPR), which results from a combination of the increased permeability of tumor blood vessels and the decreased rate of clearance caused by the lack of functional lymphatic vessels in the tumor. [69] The nanoparticles can be formulated by an emulsion of an oil in water phase for potential intracellular drug delivery.…”