Core-Sheath Electrospun Nanofibers Based on Chitosan and Cyclodextrin Polymer for the Prolonged Release of Triclosan.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

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.

Effect of Cold Plasma Treatment on Electrospun Nanofibers Properties: A Review.

Electrospinning of polymer materials is a widely used technique, providing nanofibrous mats with high surface to volume ratio and porosity, which show a great interest in many fields such as biomedical applications. However, nanofibers generally present some weakness including low mechanical resistance, poor bioactivity, or lower biocompatibility. Among the surface modification techniques described in the literature, cold plasma treatment may prevent these drawbacks and especially improve properties of electrospun nanofibers. Therefore, this review lays out the state-of-the-art of cold plasma treatment of nanofibers and, especially, its effect on the biocompatibility improvement, the immobilization/adsorption of molecules of interest, the surface grafting/cross-linking, and the use of the modified nanofibers in biomedical applications. In particular, this literature review demonstrates the positive effect of cold plasma treatment onto the mechanical, biological, or chemical properties of nanofibers. Future investigations should go further on the effects of the gas type but also on the possibility of coupling cold plasma treatment with other surface modification techniques.

Removal of toxic heavy metals from river water samples using a porous silica surface modified with a new ß-ketoenolic host.

A new hybrid adsorbent material for the efficient removal of heavy metals from natural real water solutions (Moroccan river water samples) was prepared by the immobilization of a new conjugated ß-ketoenol-pyridine-furan ligand onto a silica matrix. The thermodynamical properties including pH, adsorption isotherms, competitive adsorption, selectivity and regeneration were studied to investigate the effect of ketoenol-pyridine-furan-silica (SiNL) on the removal of Zn(II), Pb(II), Cd(II) and Cu(II) from aqueous solutions. An increase in adsorption as a function of pH and fast adsorption was reached within 25 min. The maximum sorption capacities for Zn(II), Pb(II), Cd(II) and Cu(II) were 96.17, 47.07, 48.30 and 32.15 mg·g-1, respectively. Furthermore, the material proved to be very stable - its adsorption capacity remained greater than 98% even after five cycles of adsorption/desorption. Compared to literature results, this material can be considered a high-performing remediation adsorbent for the extraction of Zn(II) from natural real water solution.

In vivo evaluation of post-operative pain reduction on rat model after implantation of intraperitoneal PET meshes functionalised with cyclodextrins and loaded with ropivacaine.

The avoidance of post-herniorrhaphy pain can be challenging for hernia repair and has the greatest impact on patient's quality of life, health care utilisation and cost to society. Visceral meshes, functionalised with an efficient drug carrier system - hydroxypropyl beta-cyclodextrin polymer (polyHPßCD) coating, were developed to give a prolonged intraperitoneal analgesic drug release. We attempted to evaluate the in vivo pain-relief efficacy of ropivacaine loaded polyHPßCD functionalised polyester meshes in a rat model of visceral pain induced by colorectal distension (CRD). In vivo safety, pharmacokinetic profile and biodegradation were measured via histological analysis and high-performance liquid chromatography, etc. The results confirmed that the polyHPßCD on the functionalised meshes has a high adsorption capacity of ropivacaine and resulted in a sustained drug release in rats after mesh implantation. This was further reaffirmed by an elevated pain threshold (30%) up to 4 days after implantation in the rat CRD model, compared to 1-2 days for non-adapted meshes. Neither polyHPßCD nor the loaded ropivacaine had a major impact on the inflammatory response. This evidence strongly suggests that polyHPßCD functionalised visceral mesh could be a promising approach for post-operative pain control by improving the intraperitoneal drug delivery and bioavailability.

Synthesis and characterization of polyampholytic aryl-sulfonated chitosans and their in vitro anticoagulant activity.

This work firstly aimed to synthesize mono- and di- sulfonic derivatives of chitosan by reductive amination reaction using respectively 2-formyl benzene sulfonic acid and 2,4 formyl benzene sulfonic acid sodium salts. The influence of the reactants molar ratio (R), aryl - substituted amino groups versus chitosan free amino groups, on the degree of substitution (DS) of both sulfonated chitosans was assessed by 1H NMR, elemental analysis, coupled conductometry-potentiometry analysis and UV spectrometry and FTIR. The influence of pH on sulfonated chitosans' properties in solution were investigated by solubility and zeta potential (ZP) studies, size exclusion chromatography equipped with MALLS detection (SEC-MALLS) and Taylor dispersion analysis (TDA). The polyampholytic character of both series was evidenced and strongly modified the solutions properties compared to chitosan. Then, the anticoagulant properties of mono- and di- sulfonic polymers were investigated by the measurement of the activated partial thromboplastin time (aPTT), Prothrombin-time (PT) and anti-(factor Xa).

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.

ß-Keto-enol Tethered Pyridine and Thiophene: Synthesis, Crystal Structure Determination and Its Organic Immobilization on Silica for Efficient Solid-Liquid Extraction of Heavy Metals.

Molecules bearing ß-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on ß-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed Claisen condensation and was characterized by EA, m/z, FT-IR, (¹H, (13)C) NMR and single-crystal X-ray diffraction analysis. The new structure was grafted onto silica particles to afford a chelating matrix which was well-characterized by EA, FT-IR, solid-state (13)C-NMR, BET, BJH, SEM and TGA. The newly prepared organic-inorganic material was used as an adsorbent for efficient solid-phase extraction (SPE) of Cu(II), Zn(II), Cd(II) and Pb(II) from aqueous solutions and showed a capture capacity of 104.12 mg·g(-1), 98.90 mg·g(-1), 72.02 mg·g(-1), and 65.54 mg·g(-1), respectively. The adsorption capacity was investigated, in a batch method, using time of contact, pH, initial concentration, kinetics (Langmuir and Freundlich models), and thermodynamic parameters (ΔG°, ΔH° and ΔS°) of the system effects.

Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60µm, allowing for incorporation inside the macropores (100µm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

Simultaneous immobilization of heparin and gentamicin on polypropylene textiles: a dual therapeutic activity.

The aim of this work was to prepare a nonwoven polypropylene (PP) textile functionalized with bioactive molecules in order to improve simultaneously anticoagulation and antibacterial properties. The immobilization of either heparin (anticoagulation agent) or gentamicin (aminoglycoside class antibiotic) alone has already been proven to be effective on PP nonwoven textiles. In this work, we managed to go further, by immobilizing both heparin and gentamicin at the same time on one unique textile. A successive immersion in different heparin and gentamicin bathes successfully led to a dual drug coated textile, as confirmed by several characterization techniques (Fourier transform infrared-attenuated total reflectance, X-ray photoelectron spectroscopy, and scanning electron microscopy). The immobilization times were varied in order to determine the best compromise between cytocompatibility, anticoagulant effect, and antimicrobial activity. Short immersion times in gentamicin solutions confer very good antimicrobial activity to the textile and avoid cytotoxicity, whereas long immersion times in heparin solution were necessary to observe a significant anticoagulant effect.

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

Organically modified silica with pyrazole-3-carbaldehyde as a new sorbent for solid-liquid extraction of heavy metals.

A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state 13C-NMR, nitrogen adsorption-desorption isotherm, BET surface area, BJH pore size, and scanning electron microscopy (SEM). The new product exhibits good chemical and thermal stability as determined by thermogravimetry curves (TGA). The new prepared material was used as an adsorbent for the solid-phase extraction (SPE) of Pb(II), Cd(II), Cu(II) and Zn(II) from aqueous solutions using a batch method, prior to their determination by flame atomic adsorption spectrometry. The adsorption capacity was investigated using kinetics and pH effects. Common coexisting ions did not interfere with separation and determination.

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.