Improved biocompatibility of a viscous bioerodible poly(ortho ester) by controlling the environmental pH during degradation

The poly(ortho ester), POE, used in this investigation, is a viscous bioero dible polymer (8 kDa), which rapidly degrades into a triol and an acidic by -product, acetic acid. In order to improve biocompatibility, we have evalua ted the addition of various basic excipients, such as sodium acetate, hydro xyapatite, calcium carbonate and magnesium hydroxide, which buffered and ne utralized the acidic degradation product and prolonged the polymer lifetime and drug release. This decrease of POE degradation rate results in a decre ased rate of formation of the acidic by-product. Similarly, a POE of higher molecular weight (14 kDa) has been tested. Sodium acetate was too hydrophi lic to affect the drug release and the biocompatibility of the polymer, whe reas the presence of magnesium hydroxide markedly prolonged the drug releas e and improved the acceptability of the polymer. The increased molecular we ight POE did not improve biocompatibility and a similar but delayed, inflam matory reaction was observed. (C) 2000 Elsevier Science Ltd. All rights res erved.