Stent coating by electrospinning with chitosan/poly-cyclodextrin based nanofibers loaded with simvastatin for restenosis prevention.

The main cause of failure of angioplasty stenting is restenosis due to neointimal hyperplasia, a too high proliferation of smooth muscle cells (SMC). The local and sustained delivery of selective pleiotropic drugs to limit SMC proliferation seems to be the hopeful solution to minimize this post surgery complication. The aim of this study is to develop a stent covered by nanofibers (NFs) produced by electrospinning, loaded with simvastatin (SV), a drug commonly used for restenosis prevention. NFs were prepared from the electrospinning of a solution containing SV and a mixture of chitosan (cationic) and ß-cyclodextrin (CD) polymer (anionic) which form together a polyelectrolyte complex that makes up the NFs matrix. First, the SV/CD interactions were studied by phase solubility diagram, DRX and DSC. The electrospinning process was then optimized to cover a self-expandable NiTiNOL stent and the mechanical resistance of the NFs sheath upon its introduction inside the delivery catheter was considered, using a crimper apparatus. The morphology, coating thicknesses and diameters of nanofibers were studied by scanning electron microscopy. The SV loading rates on the stents were controlled by the electrospinning time, and the presence of SV in the NFs was confirmed by FTIR. NFs stability in PBS pH 7.4 buffer could be improved after thermal post-treatment of NFs and in vitro release of SV in dynamic conditions demonstrated that the release profiles were influenced by the presence of CD polymer in NFs and by the thickness of the NFs sheath. Finally, a covered stent delivering 3 µg/mm2 of SV within 6 h was obtained, whose efficiency will be investigated in a further in vivo study.

Triclosan loaded electrospun nanofibers based on a cyclodextrin polymer and chitosan polyelectrolyte complex.

This work focuses on the relevance of antibacterial nanofibers based on a polyelectrolyte complex formed between positively charged chitosan (CHT) and an anionic hydroxypropyl betacyclodextrin (CD)-citric acid polymer (PCD) complexing triclosan (TCL). The study of PCD/TCL inclusion complex and its release in dynamic conditions, a cytocompatibility study, and finally the antibacterial activity assessment were studied. The fibers were obtained by electrospinning a solution containing chitosan mixed with PCD/TCL inclusion complex. CHT/TCL and CHT-CD/TCL were also prepared as control samples. The TCL loaded nanofibers were analyzed by Scanning Electron Microscopy (SEM), Fourier Transformed Infrared spectroscopy (FTIR) and X-Ray Diffraction (XRD). Nanofibers stability and swelling behavior in aqueous medium were pH and CHT:PCD weight ratio dependent. Such results confirmed that CHT and PCD interacted through ionic interactions, forming a polyelectrolyte complex. A high PCD content in addition to a thermal post treatment at 90°C were necessary to reach a nanofibers stability during 15days in soft acidic conditions, at pH=5.5. In dynamic conditions (USP IV system), a prolonged release of TCL with a reduced burst effect was observed on CHT-PCD polyelectrolyte complex based fibers compared to CHT-CD nanofibers. These results were confirmed by a microbiology study showing prolonged antibacterial activity of the nanofibers against Escherichia coli and Staphylococcus aureus. Such results could be explained by the fact that the stability of the polyelectrolyte CHT-PCD complex in the nanofibers matrix prevented the diffusion of the PCD/triclosan inclusion complex in the supernatant, on the contrary of the similar system including cyclodextrin in its monomeric form.

Multilayered textile coating based on a ß-cyclodextrin polyelectrolyte for the controlled release of drugs.

The aim of this work was to develop the formation of multilayered coating incorporating a cyclodextrin polyelectrolyte onto a non-woven polyethylene terephthalate (PET) textile support in order to obtain reservoir and sustained release properties towards bioactive molecules. We optimized the multilayer assembly immobilization onto the PET surface according to the layer-by-layer (LbL) deposition process. After a pre-treatment of the textile support aiming to offer a sufficient ionic character to the surface, it was alternatively immersed into two polyelectrolytes aqueous solutions consisting of chitosan (CHT) as polycation on the one hand, and a ß-cyclodextrin polymer (polyCTR-ßCD) as polyanion on the other hand. In a second approach, a TBBA/polyCTR-ßCD complex (4-tert-butylbenzoic acid, TBBA) was used in order to load the system with a drug model whose kinetics of release was assessed. Gravimetry, microscopy, OWLS, colorimetric titration, infrared and zetametry were used as characterization techniques. An effective deposition on the textile surface due to ionic interactions with alternation of up to 10 layers of each of both polyelectrolytes was clearly evidenced. However, we observed that layer formation occurred to a lesser extent when TBBA/polyCTR-ßCD complex was applied instead of polyCTR-ßCD alone. The release study showed that drug reservoir properties and release kinetics could be controlled by the number of layers in the system and that TBBA release was faster than the multilayered coating degradation.

High-performance liquid chromatographic enantioseparation of flavanones on 2-hydroxy- 3-methacryloyloxypropyl beta-cyclodextrin copolymer coated silica phase.

Chromatographic resolution of four flavanones is achieved by reversed-phase high-performance liquid chromatography (HPLC) on a chiral stationary phase based on silica coated with a (2-hydroxy-3-methacryloyloxypropyl beta-cyclodextrin-co-N-vinylpyrrolidone) copolymer. The influence of the mobile phase water content and the nature of the organic modifier on the retention and resolution is evaluated. Monosubstituted flavanones are better resolved than the unsubstituted one. Nevertheless, the 6- and 7-methoxy substituents enhance retention and chiral recognition to polymeric beta-cyclodextrin stationary phase less than the 6-hydroxy group.

High-performance liquid chromatographic stationary phases based on silica coated by in situ polymerization of a methacryloyl beta-cyclodextrin monomer: synthesis, characterization, and chromatographic evaluation.

Porous silica beads have been coated with a 2-hydroxy-3-methacryloyloxypropyl beta-cyclodextrin polymer by in situ free-radical polymerization in water. This system has been developed for use as a stationary phase in high-performance liquid chromatography. In the conditions used, the coating efficiency is controlled by the initial concentration of the monomer. The polymer coating has been quantitated by thermogravimetric analysis. The stationary phases have also been characterized by means of the nitrogen adsorption/desorption method, energy dispersion X-ray analysis, and scanning electron microscopy to investigate the changes in the porosity, as well as in the surface properties generated by the coating process. Finally, the chromatographic evaluation has been made under normal- and reversed-phase elution conditions.