Novel Controlled Delivery Systems for Contraceptives

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DESCRIPTION (provided by applicant): Subdermal implants for controlled delivery of contraceptive hormones have become the target of litigation in recent years for causing a variety of problems in users. These problems include purported serious side effects and complications during insertion and removal. A well-developed contraceptive hormone delivery system must limit the burst effect on injection, release the hormone within the therapeutic requirements for the duration of treatment, ease of administration, biodegradable, and cost effectiveness of the manufacturing process. Smart polymer solution based delivery systems would meet all the above requirements. The long-term goal of this project is to develop smart polymer solution based controlled delivery systems to deliver contraceptive hormones after single subcutaneous injection at predefined rate for longer duration. We propose to test the hypotheses that phase and temperature sensitive, reversibly gel forming, biodegradable, smart polymers can control the in vitro and in vivo release of hormone and the proposed smart polymer based delivery systems are biocompatible. To test our hypotheses, we plan to study the following specific aims: (1) To synthesize temperature sensitive triblock copolymers and characterize them for critical gel concentration, gel transition temperature (i.e., lower critical solution temperature), weight average molecular weight by gel permeation chromatography, and number average molecular weight by 1H NMR; (2) To prepare in situ gel forming smart polymer solution based controlled delivery systems for levonorgestrel and testosterone, using phase sensitive and temperature sensitive polymers; (3) To study in vitro release profiles of levonorgestrel and testosterone from delivery systems; (4) To evaluate the biocompatibility of the above delivery systems in vitro, using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay; and (5) To study in vivo absorption of the above hormones from delivery systems in rabbits. We believe that the present study has potential to result in novel and improved approaches for parenteral controlled release delivery systems for contraceptive hormones. Development of such a novel therapeutic system is critical for successful treatment of hormone-related diseases and improvement in the patients' quality-of-life.