Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for Photodynamic Ablation of Cancer Cells.

An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)- co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC- co-MAda)) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The hydrophobic photosensitizer chlorin e6 (Ce6) was conjugated to ß-cyclodextrin (ß-CD) by glutathione (GSH)-sensitive disulfide bonds. The Ce6 conjugated supramolecular prodrug nanocarriers were fabricated due to the host-guest interaction between adamantane and ß-CD, which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The Ce6 conjugated prodrug nanocarriers showed reduction-responsive release of Ce6, which could result in the activation of Ce6. The generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced due to the activation of Ce6. In additiona, the Ce6 conjugated prodrug nanocarriers could effectively inhibit the proliferation of cancer cells upon light irradiation.

Hierarchical supramolecular hydrogels: self-assembly by peptides and photo-controlled release via host-guest interaction.

A hierarchical supramolecular hydrogel was self-assembled from a Fmoc-RGDS tetrapeptide and showed photo-controlled release directed by host-guest interaction. Multiple payloads, including vesicles, were successively released from a single peptide hydrogel.

Bundle-shaped cyclodextrin-Tb nano-supramolecular assembly mediated by C60: intramolecular energy transfer.

A bundle-shaped nano-supramolecular assembly possessing numerous luminescent cyclodextrin-Tb polyads and photosensitizing C(60) units has been constructed through the end-to-end inclusion complexation of cyclodextrin cavities with C(60)s, and its properties have been comprehensively characterized. Further investigations on the luminescence properties of the cyclodextrin-Tb polyad and the bundle-shaped assembly demonstrate that a pyridine --> Tb --> C(60) intramolecular energy transfer process is operative when a solution of the assembly is exposed to UV light.

Bis(phenylthienyl)ethene-tethered beta-cyclodextrin dimers as photoswitchable hosts.

Two beta-cyclodextrin dimers tethered by photoswitchable bis(phenylthienyl)ethene moieties were synthesized as potentially tunable receptor molecules. The cyclodextrin cavities of these dimers were linked via their secondary sides, with the photochromic bis(phenylthienyl)ethene unit either directly connected to the secondary rim (7) or via propyl spacers (10). By irradiation with light the dimers were reversibly switched between a relatively flexible (open) form and a rigid (closed) form. The photostationary states for both dimers consisted of 92% of the open and 8% of the closed form, enabling the nearly complete conversion between the two forms. The binding properties of the open and closed forms of dimers 7 and 10 were assessed by complexation studies with meso-tetrakis(4-sulfonatophenyl)porphyrin (TSPP) using isothermal titration calorimetry. For the rigidly tethered dimer 7, a factor 8 difference in binding affinity between the open and closed form of the dimer was found. This difference in binding affinity reflects the difference in enthalpy of binding for the two dimers, indicating that the beta-cyclodextrin cavities of the closed dimer 7b are spaced too far apart from each other by the rigid closed bis(phenylthienyl)ethene tether to cooperatively bind TSPP. The difference in binding affinity was sufficient to enable the phototriggered release of TSPP from dimer. The thermodynamic parameters obtained for dimer 10 suggested that the closed tether substantially contributes to the binding of TSPP. The open and closed form of dimer 10 bound TSPP with similar association constants, although the enthalpy of binding for the complexation of TSPP by the closed form of dimer 10 was more favorable than that found for the open form of the dimer.

Spectroscopic and electrochemical study of Rose Bengal in aqueous solutions of cyclodextrins.

The interaction of Rose Bengal (RB) in aqueous solution of LiClO4 0.1 M with alpha-cyclodextrin (alpha-CD), hydroxypropyl-beta-cyclodextrins (HP-beta-CD) and hydroxypropyl-gamma-cyclodextrins (HP-gamma-CD) were studied by spectrophotometric measurements. The presence of Induced Circular Signals and the results of the analysis of the modifications in the absorbance spectra of RB produced by the presence of CDs in solution indicate that RB forms inclusion complexes only with HP-beta-CD and with HP-gamma-CD.

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.

Photostability studies on nicardipine-cyclodextrin complexes by capillary electrophoresis.

Nicardipine (NC)-cyclodextrin solid systems were prepared in equimolar ratios and their photostability in aqueous solution under exposure to UV(A)-UV(B) radiations was evaluated. The photodegradation process was monitored by a capillary electrophoresis (CE) method able to provide the enantioresolution of the rac-nicardipine. Enantioresolution was achieved using the mixture 3.0% sulfate-beta-cyclodextrin (SbetaCD) and 2.0% heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD) as chiral selector in 20mM triethanolammonium phosphate solution (pH 3.0). The photostability studies were carried out on inclusion complexes of rac-nicardipine with alpha-cyclodextrin (alphaCD), beta-cyclodextrin (betaCD), gamma-cyclodextrin (gammaCD), hydroxypropyl-alpha-cyclodextrin (HPalphaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), hydroxypropyl-gamma-cyclodextrin (HPgammaCD), (2-hydroxyethyl)-beta-cyclodextrin (HEbetaCD) and methyl-beta-cyclodextrin (MbetaCD). A photoprotective effect was observed by betaCD, HPalphaCD, HEbetaCD, whereas gammaCD, MbetaCD, HPbetaCD and HPgammaCD did not affect the nicardipine photostability. Conversely, alphaCD was found to favour the drug photodegradation. Evidences for CDs-mediated stereoselective photodegradation of rac-nicardipine were observed only for the beta-CD complex. In this case, two distinct photodegradation profiles, with two different kinetic constants (k), were observed for the nicardipine enantiomers.

Design and monitoring of photostability systems for amlodipine dosage forms.

Photostability of amlodipine (AML) has been monitored in several pharmaceutical inclusion systems characterized by plurimolecular aggregation of the drug and excipients with high molecular weight. Several formulations including cyclodextrins, liposomes and microspheres have been prepared and characterized. The photodegradation process has been monitored according to the conditions suggested by the ICH Guideline for photostability testing, by using a light cabinet equipped with a Xenon lamp and monitored by spectrophotometry. The formulations herein tested have been found to be able to considerably increase drug stability, when compared with usual pharmaceutical forms. The residual concentration detected in the inclusion complexes with cyclodextrins and liposomes was 90 and 77%, respectively, while a very good value of 97% was found for microspheres, after a radiant exposure of 11,340 kJm(-2).

Photo-responsive retention behavior of azobenzene-modified cyclodextrin stationary phase in micro-HPLC.

An azobenzene-modified gamma-cyclodextrin stationary phase (Az gamma-CDSP) was prepared and its photo- and temperature-responses for the retention of perylene and pentacene were investigated using a mixture of methanol and water as the mobile phase in micro-HPLC. The retention of perylene slightly increased, whereas that of pentacene significantly decreased by UV light irradiation to Az gamma-CDSP. These retentions recovered upon irradiation with visible light. Both retentions decreased upon an increase in the column temperature. It was presumed that the trans-azobenzene moiety acts as a preventive cap for perylene and a spacing for pentacene in filling the CD cavity. An azobenzene-modified stationary phase changed its retention behavior with the column temperature and the light irradiation. An improvement in the micro-HPLC system and the optimization of the molecular structure of the photo-responsive stationary phase would provide selective retention control by the irradiation of light in micro-separation systems.

Complex permittivities of cyclomaltooligosaccharides (cyclodextrins) over microwave frequencies to 26 GHz.

Complex permittivities (epsilon*) for microwave radiation between 0.5 and 26 GHz have been determined for alpha-, beta-, and gamma-cyclodextrins in the solid state at room temperature. For the real component of epsilon*, maxima occur near 0.6 GHz, and the relation beta > alpha > gamma is evident across the full-frequency spectrum. Dielectric loss is significant only between 5 and 12 GHz for beta- and gamma-cyclodextrins with maxima near 7.5 GHz.

Internalization of cycloheptaamylose-dansyl chloride complex during labelling of surface membrane in living Paramecium aurelia cells.

Internalization of cycloheptaamylose-dansyl chloride complex during surface labelling of living long-term starved Paramecium aurelia cells has been observed. This process may be inhibited by pretreatment of the ciliates with dichloroisoproterenol. Uptake of cycloheptaamylose-dansyl chloride may be visualized only after UV preirradiation: the appearance of orange-fluorescing vacuoles of diameter 2.3-4.5 micron may then be observed. Microspectrographic analysis performed on the cells and dansyl derivatives indicates that this fluorescence is produced by a photochemical reaction of dansyl chloride - released from CDC complex inside the digestive vacuoles-under the influence of UV irradiation.