Host Response to Long Acting Injections and Implants

Abstract

Perspectives on the in vivo biocompatibility of drug delivery systems to be considered in the design, development, and evaluation of drug delivery systems are presented. Temporal events occurring in response to the implanted/injected drug delivery system are presented, including early events following injection/implantation, acute infl ammation, chronic infl ammation, granulation tissue formation, foreign body reaction, and fi brosis/fi brous encapsulation. Both nonbiodegradable and biodegradable/resorbable systems are discussed. Important in the identifi cation of biocompatibility of any drug delivery system is the intensity and/or time duration of the various components of the infl ammatory reaction, wound healing responses, and foreign body responses. Finally, a section on immunotoxicity (acquired immunity) has been included due to current events in development of controlled sustained release systems focused on delivery of biologically reactive agents that may potentially initiate an adaptive immune response. IntroductionIn the research and development of implantable or injectable long acting drug delivery systems, in vivo biocompatibility studies play an important role in determining the safety and effi cacy of these devices. The evaluation of the biocompatibility of implantable or injectable drug delivery systems requires an understanding of the infl ammatory and healing responses of implantable materials. For delivery systems, this includes an appreciation of the infl ammatory and healing responses of degradable/resorbable systems as well as nondegradable systems. In vivo biocompatibility

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“…In inflamed eyes, vitreous membranes are facilitated by the formation of a "provisional" matrix, an exudate of serum proteins that leak into the eye, covering the device or depot, and creating a substrate for recruitment of additional leukocytes and compliment activation. 217,218 This matrix provides a substrate for vitreous membrane formation that ultimately isolate the device within the ocular space and resembles that which occurs following penetration by a foreign body. Although inflammatory cytokines appear to have an essential role in retinal and vitreous membrane formation, the presence of leukocytes is not imperative for membranes to form in the eye.…”

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