To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery.

Although a number of drug-eluting coatings for vascular stents (VSs) have been developed and are in commercial use, more efficient stent coatings and drug delivery systems are needed. Sirolimus (SRL) is a clinically important drug with antiproliferative and immunosuppressive activities that is widely used for coating stents. Here, we characterized SRL-enriched matrices, intended for coating vascular stents, that were produced by electrospinning (ES) on a drum collector from a solution of polycaprolactone (PCL) and human serum albumin (HSA), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), dimethyl sulfoxide (DMSO), and SRL. The release of tritium-labeled SRL (³H-SRL) from matrices in phosphate-buffered saline (PBS) or human blood plasma (BP) was studied. The introduction of DMSO in the ES blend decreased SRL release. The use of BP significantly accelerated SRL release through binding with serum biomolecules. The exchange of PBS or BP after every time point also increased SRL release. The maximum SRL release in BP was observed at 3 days. The matrices produced from the ES solution with DMSO and HSA released no more than 80% SRL after 27 days in BP, even under medium exchange conditions. Therefore, PCL-based matrices containing HSA, SRL, and DMSO can be used for coating VSs with prolonged SRL delivery.

Activated carbon (AC) could be potentially useful as a drug carrier in fiber polymer scaffolds destined for prolonged drug delivery. To be introduced, AC must be ground into smaller-sized particles to be introduced in scaffolds, as most biocompatible scaffolds consist of fibers with a diameter of less than 1 µm. In this study, the adsorption of sirolimus (SRL) from phosphate-buffered saline (PBS) solution and blood plasma (BP) onto AC of AX-21 type, as well as the release of SRL from AC depending on its fragmentation, were studied. Two-stage grinding of the AC, first with a ball mill, and then with a bead mill, was performed. Grinding with a bead mill was performed either in water or in polyvinylpyrrolidone to prevent aggregation of AC particles. Dynamic light scattering and scanning electron microscopy (SEM) demonstrated that the size of the particles obtained after grinding with a ball mill was 100–10,000 nm, and after grinding with a bead mill, 100–300 nm. Adsorption in PBS was significantly higher than in BP for all fractions, and depended on SRL concentration. The fraction obtained after grinding with a ball mill showed maximal SRL adsorption, both in PBS and BP, and slow SRL release, in comparison with other fractions. The 100–300 nm AC fractions were able to adsorb and completely release SRL into BP, in contrast to other fractions, which strongly bound a significant amount of SRL. The data obtained are to be used for controlled SRL delivery, and thus in the modification of drug delivery in biological media.

It was previously shown that polycaprolactone (PCL)-based electrospun-produced paclitaxel (PTX)-enriched matrices exhibit long-term drug release kinetics and can be used as coatings for drug-eluting stents (DES). The installation of vascular stents involves a twofold increase in stent diameter and, therefore, an elongation of the matrices covering the stents, as well as the arterial wall in a stented area. We studied the influence of matrix elongation on its structure and PTX release using three different electrospun-produced matrices. The data obtained demonstrate that matrix elongation during stent installation does not lead to fiber breaks and does not interfere with the kinetics of PTX release. To study PTX diffusion through the expanded artery wall, stents coated with 5%PCL/10%HSA/3%DMSO/PTX and containing tritium-labeled PTX were installed into the freshly obtained iliac artery of a rabbit. The PTX passing through the artery wall was quantified using a scintillator β-counter. The artery retained the PTX and decreased its release from the coating. The retention of PTX by the arterial wall was more efficient when incubated in blood plasma in comparison with PBS. The retention/accumulation of PTX by the arterial wall provides a prolonged drug release and allows for the reduction in the dose of the drugs in electrospun-produced stent coatings.