Partition-controlled progesterone release from waterborne, in situ-gelling materials

The primary goal of this work was to evaluate the long-term constant zero-order release of progesterone from a waterborne, in situ-gelling, injectable material. The motivation for this is to develop an intrafallopian tube embolization system for contraception. Poly(ethylene glycol) diacrylate (PEGDA, 575 g/mol) or poly(propylene glycol) diacrylate (PPODA, 540 g/mol) as a Michael-type addition acceptor was combined with pentaerythritol-tetrakis (3-mercaptopropionate; a Michael-type addition donor) to create a 75 wt.% emulsion solution in 0.1 M PBS (pH 7.4 for PEGDA and pH 12 for PPODA) that gels in minutes by the Michael-type reaction to form a hydrophobic solid. Samples, with similar to5.5 or 25 wt.% progesterone, were formed in Tygon tubing. Samples (1.6 mm x 1.0 cm cylinders) showed constant, partition-controlled release of progesterone for a prolonged period (time dependent on the mass of progesterone). Cylinders with similar to25 wt.% load of progesterone exhibited constant release (similar to40 mug per day) for more than 50 days in both the PEGDA and PPODA systems. This type of release is normally associated with preformed hydrophobic matrix systems. In contrast, these in situ-gelling materials reported here can be used to provide zero-order, partition-controlled release of progesterone and enhance the efficiency of an intrafallopian tube embolization system through progesterone release in an injectable, in situ-forming system. (C) 2004 Elsevier B.V. All rights reserved.