Novel Controlled Delivery Systems for Contraceptives

新型避孕药控释系统

基本信息

批准号：
6917096
负责人：
Jagdish Singh
金额：
$ 7.05万
依托单位：
NORTH DAKOTA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6917096
关键词：
biodegradable product biomaterial compatibility biomaterial development /preparation contraceptives copolymer drug delivery systems gel filtration chromatography high performance liquid chromatography hormone therapy laboratory rabbit levonorgestrel medical implant science nuclear magnetic resonance spectroscopy polymers subcutaneous drug administration testosterone therapy design /development

项目摘要

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.

描述（由申请人提供）：近年来，用于控制避孕激素的可控避孕激素的植入物已成为诉讼的目标，原因是用户造成了各种问题。这些问题包括在插入和去除过程中据称严重的副作用和并发症。发达的避孕激素递送系统必须限制对注射的爆发作用，在治疗期间释放治疗要求内的激素，易于给药，可生物降解以及制造过程的成本效益。基于智能聚合物解决方案的交付系统将满足上述所有要求。该项目的长期目标是开发基于智能聚合物解决方案的受控递送系统，以在单一皮下注射后以预定义的持续时间更长的持续时间提供避孕激素。我们建议测试阶段和温度敏感的，可逆的凝胶形成，可生物降解，智能聚合物可以控制激素的体外和体内释放，并且拟议的基于智能聚合物的递送系统是生物相容性的。为了检验我们的假设，我们计划研究以下特定目的：（1）合成温度敏感的三嵌段共聚物，并将其表征为临界凝胶浓度，凝胶过渡温度（即较低的临界溶液温度），重量平均分子量通过凝胶渗透而进行色谱法，数量平均分子量乘以1H NMR；（2）使用相灵和温度敏感聚合物制备基于左旋癌和睾丸激素的基于智能聚合物溶液的原位凝胶；（3）研究递送系统中左甲虫和睾丸激素的体外释放曲线；（4）使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴溴化物（MTT）测定法评估上述体外递送系统的生物相容性；（5）研究兔子输送系统中上述激素的体内吸收。我们认为，本研究有可能导致避孕激素的肠胃外释放输送系统的新颖和改进的方法。这种新型治疗系统的发展对于成功治疗与激素相关疾病的治疗和改善患者生活质量至关重要。