Cyclodextrin-functionalized cellulose filter paper for selective capture of diclofenac.

An environmentally friendly and low-cost material based on cellulose filter paper modified with ß-cyclodextrin (ß-CD) was designed to uptake and elute drugs for water purification. To carry out the work, a ß-CD derivative was first obtained through reaction of ß-CD with N-(hydroxymethyl) acrylamide (NMA), and then ß-CD-NMA was grafted on cellulose by means of the Fenton's reaction. The CD-grafted cellulose paper was characterized by ATR-FTIR analysis, SEM images, and mechanical properties. CD-functionalized (F1) and non-functionalized (NF) papers were tested in aqueous media containing an antibiotic (ciprofloxacin) or a non-steroidal anti-inflammatory drug (diclofenac) covering a wide range of salinity levels. Ciprofloxacin was similarly adsorbed by both papers through ionic interactions, while diclofenac was selectively and remarkably captured by the CD-functionalized filter (up to 25 mg g-1 from saline medium under biorelevant conditions; ca. 60 mg g-1 Langmuir isotherm model). Effects of diclofenac concentration, volume of medium, and incubation time on the amount adsorbed were investigated in detail. Elution tests involved the combination of several organic solvents and alkaline solutions and revealed that acetonitrile:NaOH 10 mM aq. solution (50:50, v/v) allows for an effective recovery of the previously trapped diclofenac. Application of ultrasounds shortened the process to 10 min. Reusability of F1 papers was also evaluated. Overall, the CD-grafted cellulose paper appears as a suitable material for bioremediation and analytical purposes.

Immobilization of antimicrobial and anti-quorum sensing enzymes onto GMA-grafted poly(vinyl chloride) catheters.

Catheter-associated infections still represent a challenging thread because of the likelihood of biofilm formation. The aim of this work was the surface modification of catheters to immobilize lysozyme and acylase under mild conditions while preserving antimicrobial and anti-quorum sensing performances. Glycidyl methacrylate (GMA) was grafted onto poly(vinyl chloride) (PVC) catheters by a pre-irradiation method. The effects of monomer concentration, pre-irradiation dose, reaction time, monomer concentration and reaction temperature were investigated. The grafting process was monitored using FTIR-ATR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and swelling data. Lysozyme was directly immobilized onto PVC-g-GMA maintaining the hydrolytic activity, which hindered Staphylococcus aureus adhesion. For acylase immobilization, the PVC-g-GMA catheters were reacted with ethylenediamine and glutaraldehyde in order to facilitate acylase covalent binding. Free acylase in solution demonstrated notably capability to act as quorum sensing inhibitor, as observed using Chromobacterium violaceum as biosensor, by degrading a wide variety of acylated homoserine lactones (AHLs), including those produced by Pseudomonas aeruginosa and Acinetobacter baumannii. Acylase-immobilized PVC-g-GMA catheters were challenged against degradation of AHLs and the activity monitored using both the biosensor and HPLC-MS. Relevantly, the functionalized catheters completely degraded all tested AHL signals, opening new ways of preventing biofilm formation on medical devices.

Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins).

Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs promotes drug release in aqueous media, but they may also play other roles such as protection of the drug against adverse agents during and after electrospinning, and retention of volatile fragrances or therapeutic agents to be slowly released to the environment. Moreover, fibers prepared with empty CDs appear particularly suitable for affinity separation. The interest for CD-containing nanofibers is exponentially increasing as the scope of applications is widening. The aim of this review is to provide an overview of the state-of-the-art on CD-containing electrospun mats. The information has been classified into three main sections: (i) fibers of mixtures of CDs and polymers, including polypseudorotaxanes and post-functionalization; (ii) fibers of polymer-free CDs; and (iii) fibers of CD-based polymers (namely, polycyclodextrins). Processing conditions and applications are analyzed, including possibilities of development of stimuli-responsive fibers.

HMDSO-plasma coated electrospun fibers of poly(cyclodextrin)s for antifungal dressings.

Electrospun mats containing cyclodextrin polymers (poly-αCD or poly-ßCD) were developed to act as wound dressings showing tunable release rate of the antifungal agent fluconazole incorporated forming inclusion complexes. Poly-αCD and poly-ßCD were prepared via cross-linking with epichlorohydrin (EPI) as water-soluble large molecular weight polymers. Then, polyCDs forming complexes with fluconazole were mixed with poly-(ε-caprolactone) (PCL) or poly(N-vinylpyrrolidone) (PVP) for electrospinning. Obtained bead-free fibers showed a random distribution, diameters in the 350-850nm range, and a variety of physical stability behaviors in aqueous environment. Mats were coated by hexamethyldisiloxane (HMDSO) plasma polymerization to create a hydrophobic layer that prevented rapid drug diffusion. HMDSO coating was evidenced by the Si content of mat surface (EDX analysis) and by the increase in the water contact angle (up to 130°). In physiological-mimicking medium, non-treated mats showed burst release of fluconazole, whereas HMDSO-coated mats sustained the release and delayed disintegration of PVP-based mats. Antifungal tests evidenced that both coated and non-coated mats efficiently inhibited the growth of Candida albicans.

Glucose cryoprotectant affects glutathione-responsive antitumor drug release from polysaccharide nanoparticles.

The aim of this work was to prepare polysaccharide-based nanoparticles (NPs) sensitive to glutathione (GSH), and to elucidate the effect of the concentration of glucose used as cryoprotectant during freeze-drying on the GSH-responsiveness. NPs were obtained via ionic interaction between negatively charged polysaccharides, chondroitin sulfate and dermatan sulfate, and the positively charged thiolated chitosan (CSSH), and crosslinking of CSSH before or after the nanoparticles formation with a disulfide-bond containing crosslinker, N,N'-bis(acryloyl)cystamine (BAC). NPs were freeze-dried with glucose at two different concentrations (0.5 and 5.0%w/w) and then characterized as methotrexate delivery systems, studying the effect of GSH concentration on drug release, efficacy against tumor cells and cellular internalization. Non-loaded NPs were highly compatible with murine fibroblasts and showed a suitable size for being used in anticancer therapy. When methotrexate-loaded NPs were freeze-dried with the highest glucose concentration, they lost their responsiveness to GSH concentration in vitro. Drug-loaded NPs were shown to inhibit the growth of tumor cells (HeLa and CHO-K1) with greater efficiency than free methotrexate, disregarding the concentration of glucose used for freeze-drying. Nevertheless, confocal microscopy studies revealed that cellular internalization of NPs freeze-dried with 5.0% glucose is more difficult than for NPs freeze-dried with lower glucose concentration. Thus, concentration of glucose cryoprotectant should be taken into account during development of NPs intended to release the drug as a function of GSH levels, due to the specific interactions of glucose with GSH.