Over the last 30 years, poly(ortho
esters) have evolved through four families, designated as POE I, POE II, POE III and POE IV. Of these, only POE IV has been shown to have all the necessary attributes to allow commercialization, and such efforts are currently underway. Dominant among these attributes is synthesis versatility that allows the facile and reproducible production of
polymers having the desired mechanical and thermal properties as well as desired erosion rates and drug release rates that can be varied from a few days to many months. Further, the
polymer is stable at room temperature when stored under anhydrous conditions and undergoes an erosion process confined predominantly to the surface layers. Important consequences of surface erosion are controlled and concomitant drug release as well as the maintenance of an essentially neutral pH in the interior of the matrix because acidic hydrolysis products diffuse away from the device. Two physical forms of such
polymers are under development. One form, solid materials, can be fabricated into shapes such as wafers, strands, or
microspheres. The other form are
injectable semi-solid materials that allow
drug incorporation by a simple mixing at room temperature and without the use of
solvents. GMP toxicology studies on one family of POE IV
polymers has been concluded, an IND filed and Phase I clinical trials are in progress. Important applications under development are treatment of
post-surgical pain,
osteoarthritis and ophthalmic diseases as well as the delivery of
proteins, including
DNA. Block copolymers of
poly(ortho ester) and poly(
ethylene glycol) have been prepared and their use as a matrix for
drug delivery and as
micelles, primarily for
tumor targeting, are being explored.