Sirolimus-Eluting Electrospun-Produced Matrices as Coatings for Vascular Stents: Dependence of Drug Release on Matrix Structure and Composition of the External Environment

Abstract

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.

Influence of Elongation of Paclitaxel-Eluting Electrospun-Produced Stent Coating on Paclitaxel Release and Transport through the Arterial Wall after Stenting

“…The addition of DMSO in the ES solution resulted in a decrease in fiber diameter. The decrease in fiber diameter for matrices containing DMSO was also shown for PCL-based matrices containing sirolimus [ 23 ].…”

“…Thus, to study PTX release from the twofold elongated matrices, they were fixed in a tensile device, and force was applied to obtain a twofold uniaxially elongated matrix. To study the effect of deformation on the structure of the matrices depending on the position between the clamps and considering Poisson’s deformation, we used a device allowing us to expand and fix the matrix with an SEM camera, as described earlier [ 23 ]. The uniaxial elongation of the matrix results in the heterogeneous deformation of the sample ( Figure 2 ) and could thus interfere with the structure of fibers located in different regions of the sample.…”

“…The microstructures of the matrices were studied via scanning electron microscopy (SEM), as described earlier [ 21 ]. To evaluate the structure after elongation, the mechanical device described in [ 23 ] was used. The matrices and stents were fixed on a sample stand using double-sided carbon tape, sputter-coated with 10 nm of gold/palladium, and analyzed using a scanning electron microscope EVO 10 (Carl Zeiss AG, Oberkochen, Germany) at an accelerating voltage of 10 kV.…”

Special Issue: Advanced Materials in Drug Release and Drug Delivery Systems

“…The papers [ 5 , 6 ] present data about multilayer films and electrospun matrices as advanced materials used in drug delivery systems. Nie et al [ 5 ] reported on the versatile layer by layer highly stable multilayer films prepared from polymer (hyaluronic acid) and inorganic–mesoporous silica nanoparticles for the delivery of FITC-labeled short peptides.…”

“…Mesoporous silica nanoparticles enhance the stability of peptides, retention properties of peptides can be modified by varying capping-layer numbers, and the release profile of small molecules can also be adjusted by adequate carrier arrangements. Nazarkina et al describe sirolimus matrices for coating vascular stents [ 6 ]. Development of stent coatings is a valid issue, as stent implantation is a frequently performed medical procedure which can initialize various reactions stimulating an inflammatory response.…”