Evaluation of Electrospun PCL-PLGA for Sustained Delivery of Kartogenin

Abstract

In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle.

Two samples from remote locations on each membrane were plasma sputter-coated with platinum and imaged on a JEOL 6500F Field Emission Scanning Electron Microscope (Peabody, MA, USA). Three images per sample were captured, and the average fiber diameter in each image was determined using SIMPoly, a MATLAB-based image analysis tool. SEM imaging was performed in the same manner for samples which had soaked in PBS for 28 days. A custom apparatus was used to measure the water contact angle as an indicator of membrane hydrophilicity/hydrophobicity. Using a CCD camera with a macro lens, the profile of a 5 µL sessile drop of distilled water was captured immediately after it was deposited onto the membrane. Water contact angles were determined using the Contact Angle plug-in to ImageJ. Membrane mechanical properties were determined by tensile testing. Strips of membrane 60 L × 4 W mm were cut using a scalpel blade. Precise width was found through computerized measurement of seven manually drawn lines using ImageJ. Thickness at three evenly-spaced locations was determined under a force of 0.01 N applied to a 2 mm flat indenter using a Biomomentum Mach-1 Micromechanical System (Laval, Québec, Canada), the same system used for tensile testing. Based on differences in the thicknesses measured at each location, uncertainty in the true thickness is estimated at 0.02 mm (membranes were typically around 0.15 mm thick). The ends of each strip were wrapped with laboratory tape and gripped such that the exposed length was approximately 35 mm. Exact gauge length was taken as the grip-to-grip separation under a preload of 0.1 N. Strips were then pulled to failure at a constant rate of 0.05 mm S1. Elastic modulus, ultimate tensile strength, and elongation at rupture were determined from the resulting stress–strain curve (n = 7 per group)

Kartogenin; electrospinning; polycaprolactone & poly(lactic-co-glycolic acid