Semi-solid hydrophobic bioerodible poly (ortho ester) for potential application in glaucoma filtering surgery

Abstract

A semi-solid poly(ortho ester) was prepared by the reaction between 1,2,6-hexanetriol and trimethyl orthoacetate. The use of a flexible triol such as 1,2,6-hexanetriol produces highly flexible polymers that have viscous behavior at room temperature. The semi-solid nature of the polymer allows the incorporation of therapeutic agents by a simple mixing procedure without the need to use solvents or elevated temperatures. The release of 5-fluorouracil (5-FU) from this semi-solid polymer was studied in vitro. The rate of drug release was controlled by changing the molecular weight and indirectly the viscosity of the polymers. Polymers with 3500, 5800, 10100, 15200, 33300 Da molecular weight were synthesized. Drug release ranging from one day for the 3500 Da to 7 days for the 33300 Da molecular weight polymer was obtained. The different procedures used to modulate the polymer molecular weight during the synthesis are described. The temperature effect on the drug loaded polymer was also studied. The results have shown that the polymer rheological properties and the 5-FU release were affected by this parameter. The rheological study has shown that the viscosity decreased with increasing temperature. In the same way, the dependence between the temperature and the drug release was shown by the fact that only 40 wt% of 5-FU was released from the 33300 Da poly (ortho ester) after 11 days at room temperature. The possibility of injecting this polymer under the conjunctiva in the glaucoma filtering surgery therapy using a hypodermic syringe was discussed in order to carry out in vivo 5-FU release studies.