PULSATILE AND DELAYED RELEASE OF LYSOZYME FROM OINTMENT-LIKE POLY(ORTHO ESTERS)

Poly(ortho esters) have been prepared by the reaction between 1,2,6-hexanetriol and various alkyl ortho esters. Because such polymers have very flexible chains, they are viscous, ointment-like materials at room temperature. Because therapeutic agents can be incorporated into such materials by a simple mixing procedure at room temperature and without the use of solvents, they are of particular interest for the controlled release of proteins. When lysozyme, used as a model protein, was incorporated into the ointment, release occurred only after an induction period that varied from less than one day to more than 30 days. The length of the delay time was found to depend on polymer molecular weight and the nature of the alkyl substituent of the polymer. No loss of activity of the enzyme, as measured by rate of lysis of Micrococcus lysodeikticus, was noted. Thus, this system has potential usefulness for the pulsatile release of proteins.