Development and Evaluation of a Biodegradable Drug Delivery System

摘要

The goal of this program was the development of biodegradable drug delivery systems that could be implanted subcutaneously, where they would continously release antifertility agents at effective levels for periods as short as six months to as long as one year. It was desired that the delivery systems would biodegrade as soon as possible after they were exhausted of drug. Efforts were aimed at developing rapidly degradable polypeptides based upon esters of glutamic acid, with emphasis on copolymers of glutamic acid and ethyl glutamate (i.e., Glu/EGlu copolymers). Facile synthesis techniques were established. Delivery systems composed of Glu/EGlu copolymers and progestational steroids release the drug at relatively constant rates for prolonged periods of time. For example, matrix rods, (1.3 cm in length, 0.23 cm in diameter) of 29/71 Glu/EGlu containing 50% steroid by weight, released progesterone at approximately 200 micrograms/day for six months, norethisterone at approximately 110 micrograms/day for 11 months, and norgestrel at 40 to 80 micrograms/day for 15 months. Gross examination of Glu/EGlu in implant sites in mice, rats, and rabbits revealed little or no adverse tissue reaction; histopathological examination confirmed these results.