Evaluation of flexible PDL/LA based implants for sustained delivery of ciprofloxacin.

摘要

Infections in the skeletal system require high dose antibiotics for longer periods of time. Often poor perfusion at the site of infection/injury impair prognosis in many cases. In such instances localized delivery of antibiotics seems to be a better alternative. Conventional non-biodegradable delivery systems like poly methyl methacrylate (PMMA) beads loaded with antibiotics (Septopal®, Biomet, Finland) or PMMA cement require a second surgery for removal of the non biodegradable carrier. Using biodegradable polymers is more likely to improve patient compliance. Poly-DL/L-lactide (PDL/LA) is biodegradable polyester which forms lactic acid as it degrades. It is a rigid polymer with high compressive moduli often used in scaffolding applications. This rigidity often limits the use of PDL/LA in application which requires softer and more flexible delivery systems e.g. into incongruous necrotic tissue. Poly-ϵ-caprolactone (PCL) is also a polyester polymer biodegradable into 5-hydroxy caproic acids. PCL has a high elongation potential (300-500%) and is relatively less rigid than PLLA Copolymers of PDL/LA-PCL (8515LPCL, 7525LPCL and 7525DLPCL) have been investigated in this research for their potential use as biodegradable carriers for antibiotics applicable to such bone infections e.g. osteomyelitis. Comparison of copolymer properties to their respective homopolymers has also been achieved.;Implants were designed for studies using three methods of fabrication – compression, heat molding and solvent evaporation-molding. Effect of implant design method on the thermo mechanical properties of the polymers was investigated. PLLA resulted in a threefold higher compressive modulus in heat molding vs. solvent evaporation-molding. Similarly these implants were also studied for their in vitro erosion properties and macrophage (CRL2192) adhesion. Thermo mechanical characterization, change in pH and gravimetric analysis was performed at every stage of erosion study. 7525DLPCL proved to have soft flexible consistency and lowest compressive modulus (0.1MPa). Additionally 7525DLPCL was completely amorphous throughout the study period and eroded over a period of 6 weeks.;7525DLPCL was selected for further studies which involved addition of an antibiotic – ciprofloxacin hydrochloride (CIP) at varying drug loadings and evaluation of drug release from the implants for a long period of time (12 weeks). Similarly macrophage adhesion was studied as a function of CIP loading. Thermal properties were also monitored for the 6 week period and % mass lost was determined. Release of CIP was modeled using various modified sigmoidal equations and best fit was adjudged. These studies indicate good prospects of developing 7525DLPCL based soft tissue delivery systems which could be used in incongruous necrotic cavities. Investigated system appears to have requisite thermo mechanical characteristics and in vitro erosion properties which could be used for skeletal drug delivery.