Comprehensive properties of photodynamic antibacterial film based on κ-Carrageenan and curcumin-ß-cyclodextrin complex.

In this study, a biodegradable photodynamic antibacterial film (Car-Cur) was prepared using casting method with κ-Carrageenan (κ-Car) as film-forming substrate and curcumin-ß-cyclodextrin (Cur-ß-CD) complex as photosensitizer. The comprehensive performance of this Car-Cur film was investigated. The obtained results showed that the concentration of Cur-ß-CD was an important factor determining the properties of film including tensile strength (TS) elongation at break (EB), water vapor permeability (WVP), water content (WC) and thermal stability. When the concentration of Cur-ß-CD is 1%, the film demonstrated the maximum TS and EB, increased thermal stability, with desirable WVP and WC. Furthermore, this film also showed good photodynamic antibacterial potential against Staphylococcus aureus and Escherichia coli upon irradiation of blue LED light. Moreover, the film can be degraded in the soil in one week. In conclusion, our results suggested Car-Cur photodynamic film could be developed as biodegradable antimicrobial packaging material for food preservation.

Novel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized ß-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy.

Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, ß-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated ß-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chemistry.

One-pot synthesis of ß-cyclodextrin modified Au nanoclusters with near-infrared emission.

ß-Cyclodextrin modified gold nanoclusters (AuNCs@ß-CD) with near-infrared (NIR) emission were facilely and successfully prepared based on a one-pot and green synthesis route, which provides an interesting and efficient strategy to realize NIR emissive nanoclusters via supramolecular macrocycle modification.

Bright G-Quadruplex Nanostructures Functionalized with Porphyrin Lanterns.

The intricate arrangement of numerous and closely placed chromophores on nanoscale scaffolds can lead to key photonic applications ranging from optical waveguides and antennas to signal-enhanced fluorescent sensors. In this regard, the self-assembly of dye-appended DNA sequences into programmed photonic architectures is promising. However, the dense packing of dyes can result in not only compromised DNA assembly (leading to ill-defined structures and precipitates) but also to essentially nonfluorescent systems (due to π-π aggregation). Here, we introduce a two-step "tether and mask" strategy wherein large porphyrin dyes are first attached to short G-quadruplex-forming sequences and then reacted with per-O-methylated ß-cyclodextrin (PMßCD) caps, to form supramolecular synthons featuring the porphyrin fluor fixed into a masked porphyrin lantern (PL) state, due to intramolecular host-guest interactions in water. The PL-DNA sequences can then be self-assembled into cyclic architectures or unprecedented G-wires tethered with hundreds of porphyrin dyes. Importantly, despite the closely arrayed PL units (∼2 nm), the dyes behave as bright chromophores (up to 180-fold brighter than the analogues lacking the PMßCD masks). Since other self-assembling scaffolds, dyes, and host molecules can be used in this modular approach, this work lays out a general strategy for the bottom-up aqueous self-assembly of bright nanomaterials containing densely packed dyes.

Mannoside and 1,2-mannobioside ß-cyclodextrin-scaffolded NO-photodonors for targeting antibiotic resistant bacteria.

Two ß-cyclodextrin derivatives randomly appended on the primary face with both the nitric oxide (NO) photodonor 4-nitro-3-(trifluoromethyl)aniline and a mannose or α(1→2)mannobioside residue are reported to construct targeted NO photoreleasing nanocarriers. 2D ROESY and PGSE NMR suggested supramolecular homodimerization in water by inclusion of the nitroaniline group into the facing macrocycle cavities. Isothermal titration calorimetry on their concanavalin A lectin binding showed an exothermic binding event to the lectin and an endothermic process during the dilution of the conjugates. Both α(1→2)mannobioside and the nitroaniline moieties significantly enhanced the binding to the lectin. These effects might arise from a better fit within the carbohydrate-recognition site in the former case and a multivalent effect caused by homodimerization in the latter. Direct detection of NO by amperometric technique shows that both ß-cyclodextrin derivatives release this radical upon excitation with visible light with higher efficiency than the unfunctionalized NO photodonor.

In vitro photobiochemical characterization of sulfobutylether-ß-cyclodextrin formulation of bufexamac.

The present study aimed to modulate the photoreactivity of bufexamac, with a focus on photostability and phototoxicity, by forming an inclusion complex with sulfobutylether-ß-cyclodextrin (SBECD). The photobiochemical properties of bufexamac were evaluated by reactive oxygen species (ROS) assay and using in vitro photogenotoxic assessment tools. To assess the inclusion properties of SBECD complex with bufexamac, a UV absorption spectroscopic study was also carried out. The influence of SBECD on the photoreactivity of bufexamac was analyzed by ROS assay and photostability test. From the photobiochemical data, superoxide generation from irradiated bufexamac indicated its photoreactivity; however, the photogenotoxic risk of bufexamac was negligible owing to low DNA-binding affinity and DNA-photocleaving activity. SBECD complex of bufexamac was formed, and the association constant of the complex was calculated to be 620M(-1). On the basis of the photochemical data on bufexamac co-existing with SBECD, ROS generation from irradiated bufexamac (200µM) was inhibited by SBECD at concentrations of over 20µM. The degradation constant of bufexamac in SBECD was decreased ca. 30% compared with that of bufexamac, suggesting improvement of its photostability. The phototoxic risk of bufexamac might be attenuated by SBECD complexation, and cyclodextrin inclusion complexes might be a useful approach for modulating the phototoxicity of drugs.

Stereoselective interaction of ketoprofen enantiomers with ß-cyclodextrin: ground state binding and photochemistry.

The chiral recognition ability of ß-cyclodextrin (ß-CyD) vs.S- and R-ketoprofen (KP) enantiomers has been studied by circular dichroism (CD), isothermal titration calorimetry (ITC) and NMR. The association constants of the 1 : 1 complexes obtained from CD and ITC titration experiments resulted to be the same for both enantiomers within the experimental uncertainty. Well differentiated CD spectra were determined for the diastereomeric complexes. Their structure was assessed by molecular mechanics and molecular dynamics calculations combined with quantum mechanical calculation of the induced rotational strengths in the low energy KP:ß-CyD associates, upon comparison of the calculated quantities with the corresponding experimental CD. The inclusion geometry is similar for both enantiomers with the aromatic carbonyl inserted in the CyD cavity, the monosubstituted ring close to the primary CyD rim and the carboxylate group exposed to the solvent close to the secondary rim. NMR spectra fully confirmed the geometry of the diastereomeric complexes. Tiny structural differences were sensibly probed by CD and confirmed by 2D ROESY spectra. Photoproduct studies with UV absorption and MS detection as well as nanosecond laser flash photolysis evidenced lack of chiral discrimination in the photodecarboxylation of KP within the cavity and formation of a photoaddition product to ß-CyD by secondary photochemistry of 3-ethylbenzophenone.

Formation and energy transfer property of a subphthalocyanine-porphyrin complex held by host-guest interactions.

A stable 2 : 1 host-guest complex is formed between a beta-cyclodextrin-conjugated subphthalocyanine and a tetrasulfonated porphyrin in water. The complex exhibits an energy transfer property from the excited subphthalocyanine to the porphyrin core with an excitation energy transfer quantum yield of 0.38.

Assembling a mixed phthalocyanine-porphyrin array in aqueous media through host-guest interactions.

A stable 1:1 host-guest complex is formed between a silicon(IV) phthalocyanine conjugated axially with two permethylated beta-cyclodextrin units and a tetrasulfonated porphyrin. The complex exhibits a light-harvesting property and works as an efficient photosensitizing system, killing HT29 human colon adenocarcinoma cells with an IC50 value of 0.09 microM. [structure: see text].

Photostabilization of 1,4-dihydropyridine antihypertensives by incorporation into beta-cyclodextrin and liposomes.

Inclusion compounds of eleven dihydropyridine drugs were formed and investigated for protection against photo-induced drug degradation. Formulations of cyclodextrins and liposomes were prepared and their photoprotective ability for the encapsulated drug was monitored. Drug photodegradation was spectrophotometrically followed during exposure of the formulations to light of a Xenon lamp. ICH guidelines for photostability testing were applied. A comparison with common pharmaceutical formulations revealed optimal protection for both formulations. The use of the liposome and cyclodextrin inclusion complexes resulted in a mean drug recovery of 77 and more then 90% respectively, after a light exposure until to 30 minutes with an intensity of 21 kJ x min(-1) m(-2). Lercanidipine and Manidipine only did not show a satisfactory increase of photostabilization in the studied supramolecular complexes, due to their low inclusion in both the systems.

Single- and multi-photon excited fluorescence from serotonin complexed with beta-cyclodextrin.

The fluorescence of serotonin on binding with beta-cyclodextrin has been studied using both steady state and time-resolved methods. Steady state fluorescence intensity of serotonin at 340 nm showed approximately 30% increase in intensity on binding with K(A) approximately 60 dm(3) mol(-1) and the fluorescence lifetimes showed a corresponding increase. In contrast, the characteristic green fluorescence ('hyperluminescence') of serotonin observed upon multiphoton near-infrared excitation with sub-picosecond pulses was resolved into two lifetime components assigned to free and bound serotonin. The results are of interest in relation to selective imaging and detection of serotonin using the unusual hyperluminescence emission and in respect to recent determinations of serotonin by capillary electrophoresis in the presence of cyclodextrin. The results also suggest that hyperluminescence occurs from multiphoton excitation of a single isolated serotonin molecule.

Sterile, injectable cyclodextrin nanoparticles: effects of gamma irradiation and autoclaving.

Sterility is required as stated by compendial requirements and registration authorities worldwide for an injectable drug carrier system. In this study, injectable nanospheres and nanocapsules prepared from amphiphilic beta-cyclodextrin, beta-CDC6, were assessed for their in vitro properties such as particle size distribution, zeta potential, nanoparticle yield (%), drug entrapment efficiency and in vitro drug release profiles. Different sterilization techniques such as gamma irradiation and autoclaving were evaluated for their feasibility regarding the maintenance of the above mentioned nanoparticle properties after sterilization. It was found that amount these techniques, sterilization with gamma irradiation seemed to be the most appropriate technique with no effect on particle size, drug loading and drug release properties. Gamma irradiation causes some chemical changes on beta-CDC6 observed as changes in zeta potential but this does not lead to any significant changes for nanoparticle properties. Autoclaving caused massive aggregation for the nanoparticles followed by precipitation, which led to the conclusion that excessive heat disrupted nanoparticle integrity. Sterile filtration was not feasible since nanoparticle sizes were larger than the filter pore size and the yield after sterilization was very low. Thus, it can be concluded that blank and drug loaded beta-CDC6 nanospheres and nanocapsules are capable of being sterilized by gamma irradiation.

Facile light-triggered one-step synthesis of small and stable platinum nanoparticles in an aqueous medium from a beta-cyclodextrin host-guest inclusion complex.

It is shown, for the first time, that small (ca. 2 nm) and stable platinum nanoparticles can be easily obtained in one step through visible light irradiation of a host-guest inclusion complex between beta-cyclodextrin and platinum acetylacetonate in a water solution. The exclusive control of the reaction by an external trigger, the removal of the undesired reaction products without any manipulation of the sample, and the absence of ionic repulsions between the metal nanoparticles represent the main remarkable advantages offered by this synthetic methodology.

Properties of eight methacrylated beta-cyclodextrin composite formulations.

OBJECTIVES: Methacrylated beta-cyclodextrins (MCDs) are novel candidate dental monomers if all or some of the hydroxyl groups of beta-cyclodextrin are substituted with methacrylate groups. The main objective of this study was to evaluate mechanical properties of a number of composite formulations having MCDs as novel dental comonomers. The properties determined were flexural strength (FS), volumetric shrinkage (VS), and degree of conversion (DC). METHODS: A mass fraction of 50% of MCD monomers was mixed with a mass fraction of 50% each of a series of dimethacrylate or monomethacrylate diluent comonomers to produce consistent formulations of a workable viscosity. For comparison a resin mixture of a mass fraction of 50% Bis-GMA and a mass fraction of 50% triethyleneglycol dimethacrylate (a typical dental resin mixture) was also studied. The mixtures were activated with camphorquinone and ethyl 4-dimethylamino benzoate. One part by mass of each activated resin formulation was mixed with three parts by mass of glass filler. Samples for the FS tests were prepared in (2 x 2 x 25) mm3 molds by light-curing the composites for 2 min on each side. The cured samples were immersed in 37 degrees C water for 24 h, and FS was measured with an Instron machine at a crosshead speed of 0.5 mm/min. VS was measured by a computer-controlled mercury dilatometer. DC was measured by near-infrared spectroscopy. RESULTS: The properties of the MCD-based composites depended on the kind of diluent used. With these MCD monomers, diluents of triethyleneglycol dimethacrylate, 1,10-decamethylenediol dimethacrylate, or benzyl methacrylate yielded the best composite properties. SIGNIFICANCE: Although not yet fully optimized, MCD-based composite formulations containing triethyleneglycol dimethacrylate, 1,10-decamethylenediol dimethacrylate, or benzyl methacrylate yielded flexural strength and volumetric shrinkage values were comparable to those of the Bis-GMA/triethyleneglycol dimethacrylate controls. These findings lend support for further development and evaluations of polymerizable cyclodextrin derivatives for use in dental materials.

Photophysical and electrochemical properties of chlorophyll a-cyclodextrins complexes.

In this work, we have studied the interactions between two different cyclodextrins (CDs) and chlorophyll a (Chl a) in the presence of electrolyte by means of absorption, fluorescence spectroscopy, circular dichroism and cyclic voltammetry. The results obtained indicate that the presence of both CDs gives rise to an increase of Chl a solubility in water. In particular, heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin (TRIMEB) favours the dissolution of Chl a monomer in aqueous solution, whereas the presence of hydroxypropyl-beta-cyclodextrin (beta-HP-CD) promotes the pigment aggregation.

Photocontrolled release and uptake of a porphyrin guest by dithienylethene-tethered beta-cyclodextrin host dimers.

Two photoswitchable dithienylethene-tethered beta-cyclodextrin dimers were synthesized to function as host molecules with an externally controllable binding affinity. The cyclodextrin cavities of these dimers are linked through their secondary sides by a photochromic dithienylethene unit that is connected to the secondary rim either directly (4) or through propyl spacers (9). Irradiation with light switches these dimers between a relatively flexible (open) and a rigid (closed) form. The binding properties of the dimers depend on the configuration of the dithienylethene spacer, as is shown by microcalorimetry performed with tetrakis-sulfonatophenyl porphyrin (TSPP) as a guest molecule. The differences in binding properties are most pronounced for the more rigid dimer 4, which binds TSPP 35 times more strongly in the open form (4 a) than in the closed form (4 b). The values found for the enthalpy of binding (deltaH degrees ) indicate that this difference in binding is due to the loss of cooperativity between the two beta-cyclodextrin cavities in the closed form. Molecular modeling shows that 4 b is not able to bind TSPP effectively in both cyclodextrin cavities. The open and closed forms of the more flexible dimer 9 show no substantial difference in their binding of TSPP. Thermodynamic values indicative of strong binding of TSPP by two beta-cyclodextrin cavities were measured for both forms of the dimer, and molecular modeling confirms that both are flexible enough to tightly bind TSPP. The binding differences between the forms of dimer 4 allow the photocontrolled release and uptake of TSPP, which renders control of the ratio of complexed to free TSPP in solution possible.