Pharmaceutical implants: Drug incorporated antimicrobial sutures for medical applications.

摘要

Surgical Site Infections (SSIs) are common post-operative complications that patients acquire in a hospital environment during the course of treatment for other medical conditions. In surgical wounds, bacteria usually proliferate and in combination with the patient's vulnerable immune system, they can create infections that require additional medical care. Dispersion of a pharmaceutical agent into a polymeric fiber can eliminate the development of SSTs via immediate inhibition of bacterial growth caused by the sustained localized delivery of the drug molecule at the infected site, increasing its bioavailability.;In this research, the first study begins with the design and development of Polyethyleneco-Vinyl Acetate (EVA) surgical sutures incorporated with Tetracycline Hydrochloride (TC HC1) for superficial tissue bonding. The fibers were prepared at a drug / polymer ratio of 25% / 75% via the extrusion technique on a Davis Standard DS-1 OHM single screw extruder. Two different temperature profiles were applied and fibers of two different diameters and drug dispersions were collected (EVA 1 and EVA 2). TGA analysis was used to investigate their drug / polymer ratio. SEM images were taken to measure the exact diameter of the fiber samples and tensile testing proved their ability as surgical sutures.;The second study examined the quantity of TC HC1 released from the EVA I and EVA 2 fibers over a 10-day period. UV readings confirmed that sufficient amount of drug left the polymeric matrix during that time and Fick's second law of diffusion indicated anomalous, non-fickian diffusion model by both the fibers, with the EVA 2 fiber performing a release profile closer to Fickian. Antibacterial studies showed successful Escherichia Coli (E. Coli) inhibition of three different lengths (5, 10, 15cm) of both the fiber samples in the three following cases: when the fibers were left in liquid cultures for a 48-hour period, when the fibers were introduced to fresh bacteria every 24 hours and when the fibers were immersed in E. Coli cultures of higher concentrations. Cytotoxicity testing towards two different types of blood cells (HL-60, NB-4) confirmed the biocompatibility of the EVA as polymeric material.;The third study involved the design and development of Polycaprolactone (PCL) surgical sutures incorporated with TC HC1 for internal tissue bonding. The fibers were prepared at a drug / polymer ratio of 25% / 75% via the extrusion technique on the same extruder. Two different temperature profiles were applied and fibers of two different diameters and drug dispersions were collected (PCL 1 and PCL 2). TGA analysis confirmed their drug / polymer ratio. SEM images were used to measure the fibers' diameters. Tensile testing proved their potential as surgical sutures.;The fourth investigation examined the quantity of TC HC1 released from both the PCL 1 and 2 fibers over a period of 10 days. PCL 1 fiber performed an anomalous diffusion while PCL 2 fiber showed Fickian diffusion profile. Antibacterial studies on three different lengths of both the fibers (5, 10, 15cm) proved their bacterial inhibition abilities against E. Coli , when the fibers were left in liquid cultures for 48 hours, when they were introduced into fresh bacterial cultures every 24 hours and when they were immersed in liquid cultures of higher concentrations. Cytotoxicity data confirmed the PCL's biocompatible properties as a medical device component since this allowed regular cell growth of two different types of blood cells (HL-60, NB-4).