ABSTRACT
YIE W. CHIEN / Rutgers-The State Univers i ty of New J e r s e y , Piscataway, New Je r sey
I . Introduct ion 482
II . Historical Development 48 2
I I I . Approaches to Development of Implantable Therapeut ic Systems 484 A. Controlled Drug Release by Diffusion 485 B . Controlled Drug Release by Activation 498
IV. Benefits of Controlled Drug Administration Via Implantation 509
V. Medical Aspects of Implantation 512
A. The Environment of Living Tissues 512 B . Reactions of Host to Implant 513 C. Reactions of Implant to Host 515 References 516
I. INTRODUCTION
Lafarge pioneered, in 1861, the concept of implantable therapeutic systems for long-term, continuous drug administration with the development of a subcutaneously implantable drug pellet. The technique was then rediscovered in 1936 by Deanesly and Parkes [1 ,2] , who administered crystalline hormones in the form of solid steroid pellets to mimic the steady, continuous secretion of hormones from an active gland for hormone substitution therapy [3],
The subcutaneous release rate of steroids from the pellet implantation was found to be slowed down and the hormonal activities were prolonged by dispersing the steroids in cholesterol matrix during pellet fabrication [4] . Unfortunately, it was observed that the subcutaneous absorption of steroids from the cholesterol pellets varies greatly from one condition to another. The subcutaneous drug administration by pellet implantation method was then subjected to modifications by several investigators [5 ,6] .
