Tubular Electrospun Vancomycin-Loaded Vascular Grafts: Formulation Study and Physicochemical Characterization

Abstract

This work aimed at formulating tubular grafts electrospun with a size < 6 mm and incorporating vancomycin as an antimicrobial agent. Compared to other papers, the present study succeeded in using medical healthcare-grade polymers and solvents permitted by ICH Topic Q3C (R4). Vancomycin (VMC) was incorporated into polyester synthetic polymers (poly-L-lactide-co-poly-ε-caprolactone and poly lactide-co-glycolide) using permitted solvents; moreover, a surfactant was added to the formulation in order to avoid the precipitation of VMC on fiber surface. A preliminary preformulation study was carried out to evaluate solubility of VMC in different aqueous and organic solvents and its stability. To reduce size of fibers and their orientation, we studied a solvent system based on methylene chloride and acetone (DCM/acetone), at different ratios (80:20, 70:30, and 60:40). Considering conductivity of solutions and their spinnability, solvent system at a 80:20 ratio was selected for the study. SEM images demonstrated that size of fibers, their distribution, and their orientation were affected by the incorporation of VMC and surfactant into polymer solution. Surfactant allowed for the reduction of precipitates of VMC on fiber surface, which are responsible of the high burst release in the first six hours; the release was mainly dependent on graft structure porosity, number of pores, and graft absorbent capability. A controlled release of VMC was achieved, covering a period from 96 to 168 h as a function of composition and structure; the concentration of VMC was significantly beyond VMC minimum inhibitory concentration (MIC, 2 ug/mL). These results indicated that the VMC tubular electrospun grafts not only controlled the local release of VMC, but also avoided onset of antibiotic resistance.

Electrospun Naringin-Loaded Fibers for Preventing Scar Formation during Wound Healing

“…The chromatographic analysis was conducted in triplicate for each sample, and DC and EE% values were expressed as average ± standard deviation, n = 3. Drug content is expressed in µg/mg and was calculated by Equation (5), [ 24 ]: …”

Shape-Memory Polymers Hallmarks and Their Biomedical Applications in the Form of Nanofibers

“…Artificial vascular graft could be a solution for treating vascular disorders and endothelial cell dysfunction. However, a rapid formation of a confluent endothelial monolayer onto the lumen of 3D structure is essential in order to achieve a suitable regenerative process [96]. To reach this goal, novel shape-morphing scaffolds were developed, enabling programmed deformation from planar shapes to small-diameter tubular shapes, and were designed combining a biocompatible shape-memory polymer with an electrospun nanofibrous membrane [97].…”

A Review: Textile Technologies for Single and Multi‐Layer Tubular Soft Tissue Engineering

“…[82] Hence, long-chain biopolymer fibers ensure a high similarity with the native ECM, thus readily interacting with the biological system. [82] In recent studies, a wide variety of biopolymers have been used to construct scaffolds, including silk, [23,24,87] collagen/PCL, [84,88] gelatin composites, [26,89,90] PCL, [79,91,92] PCL composites [11,21,[93][94][95] PGA, [16] PVA [18] and others. Biopolymers can be of natural or synthetic origin.…”

“…[13,79,89,90] The electrospinning process parameters, in turn, control fiber alignment. [93,94] Further primary considerations entail the material properties to enhance the biomechanical and biochemical characteristics for better dimensional stability, elasticity or faster degradation rate, and increased biocompatibility.…”