ABSTRACT
INTRODUCTION In the research and development of implantable drug delivery systems, in vivo biocompatibility studies play an important role in determining the safety (biocompatibility) and efficacy (function) of these devices. The purpose of this review is to present perspectives on the in vivo tissue responses and biocompatibility of implantable drug delivery systems as they may affect the pharmacokinetics, pharmacodynamics, and metabolism of proteins and peptides. The evaluation of the biocompatibility of implantable delivery systems requires an understanding of the inflammatory and healing responses induced by implantable materials. For delivery systems, this includes an appreciation of the inflammatory and healing responses to degradable/resorbable systems as well as nondegradable systems. In this overview, tissue/material interactions and the foreign body reaction are viewed from the classical medical perspective of the pathologist. Tissue/material interactions are commonly referred to as the tissue response continuum, which is the series of responses that are initiated by the implantation procedure, as well as by the presence of the biomaterial, medical device, or drug delivery system. In this chapter, we divide the continuum of tissue/material responses into the early, transient tissue responses and the late, persistent tissue responses. Early, transient tissue/material responses include injury, blood/material interactions, provisional matrix formation, temporal sequence of inflammation and wound healing, acute inflammation, chronic inflammation, and granulation tissue development. These responses are usually of short duration, occurring over the first two to three weeks following implantation of a medical device or drug delivery system. Late, persistent tissue responses include macrophage interactions, foreign body giant cell (FBGC) formation and interactions, and fibrosis and fibrous encapsulation of the drug delivery system. The early, transient tissue responses form the basis for safety or biocompatibility considerations of the medical device or drug delivery system. Late, persistent tissue/material responses, while important to the safety and biocompatibility considerations, may be more important in modulating the performance characteristics of the drug delivery system.
