Transport Characteristics of a Novel Local Drug Delivery System Using Nordihydroguaiaretic Acid (NDGA)-Polymerized Collagen Fibers

Abstract

Local delivery of a drug in vivo would permit high interstitial drug concentration at the desired location without producing high systemic drug levels. Previous local drug delivery systems have included biodegradable polymer implants, hydrogels, and osmotic pumps [1]. In this paper, we describe a novel local drug delivery system using nordihydroguaiaretic acid (NDGA)-polymerized collagen fibers. NDGA collagen fibers were originally developed for use as biocompatible tendon bioprostheses [2]. The NDGA collagen fibers were loaded with either: dexamethasone, a synthetic glucocorticoid with anti-inflammatory and immunosuppressive activities; or dexamethasone 21-phosphate, a water soluble pro-drug that is converted into dexamethasone in vivo. Dexamethasone was chosen as the loading agent since experiments pairing the loaded fibers with implantable glucose sensors will be performed in the future. This may be useful for preventing inflammation around implantable glucose sensor [3]. This decrease in inflammation is expected to increase glucose sensor function and lifetime. We also determined the diffusion coefficient of dexamethasone and dexamethasone 21-phosphate in the NDGA collagen fiber. In an effort to control the rate of release of dexamethasone, the biocompatible copolymer, polylactic-co-glycolic acid (PLGA) was used to coat the fibers. The information obtained from these experiments is necessary for the future development of an optimal local delivery system of dexamethasone using NDGA collagen fibers in an effort to suppress the inflammatory response around implantable glucose sensors.