RECENT DEVELOPMENTS IN THE SYNTHESIS AND UTILIZATION OF POLY (ORTHO ESTERS)

One family of poly(ortho esters) can be prepared by the reaction of diketene acetals and diols. This polymer has recently been used in the development of bioerodible implants for the release of the antineoplastic agent 5-fluorouracil (5-FU) and the narcotic antagonist naltrexone. Polymer erosion was found to depend on both the nature of the acidic excipient used to control erosion rate and on the composition of the polymer. Good control over rate of release of 5-FU was achieved by using suberic acid and a polymer based on 1,6-hexanediol. Preliminary encouraging survival times have been obtained with mice inoculated with L1210 leukaemia. Polymers with a 50 wt% loading of naltrexone pamoate have been shown to release the drug by good zero order kinetics and in vivo studies are currently in progress. Another family of poly (ortho esters) can be prepared by a transesterification reaction between a triol and a trialkyl ortho ester. When the transesterification reaction is carried out with flexible triols such as 1,2,6-hexanetriol, ointment-like materials are obtained even though molecular weight can be in excess of 50,000. Release of therapeutic agents from such ointments can also be controlled with acidic excipients. Such materials are particularly useful for peptide release because these can be incorporated into the polymer at room temperature without the use of solvents. Preliminary indications of retention of activity have been obtained.