Cyclodextrin Inclusion Complexes Research Articles

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer.

Drug repositioning refers to the identification of new therapeutic indications for drugs already approved. Albendazole and ricobendazole have been used as anti-parasitic drugs for many years; their therapeutic action is based on the inhibition of microtubule formation. Therefore, the study of their properties as antitumor compounds and the design of an appropriate formulation for cancer therapy is an interesting issue to investigate. The selected compounds are poorly soluble in water, and consequently, they have low and erratic bioavailability. In order to improve their biopharmaceutics properties, several formulations employing cyclodextrin inclusion complexes were developed. To carefully evaluate the in vitro and in vivo antitumor activity of these drugs and their complexes, several studies were performed on a breast cancer cell line (4T1) and BALB/c mice. In vitro studies showed that albendazole presented improved antitumor activity compared with ricobendazole. Furthermore, albendazole:citrate-β-cyclodextrin complex decreased significantly 4T1 cell growth both in in vitro and in vivo experiments. Thus, new formulations for anti-parasitic drugs could help to reposition them for new therapeutic indications, offering safer and more effective treatments by using a well-known drug.

A review on thermal analyses of cyclodextrins and cyclodextrin complexes

Cyclodextrins are valuable natural or synthetically modified cyclic oligosaccharides that are widely used for ameliorating properties of biologically active compounds such as food additives and ingredients or medicinal compounds. They protect these compounds against light and oxidative degradation and provide host–guest supramolecular complexes having controlled release properties by molecular encapsulation, enhancing the water solubility and bioavailability. Among many characterization methods that are applicable in both solution and solid state, thermal techniques were widely used for analysis and stability evaluation of cyclodextrins and cyclodextrin complexes. This updated review deals with the use of thermal methods for analysis of cyclodextrins and cyclodextrin complexes. Classical and modern thermal techniques used for evaluation of inclusion compound formation were reviewed. Special attention was gave for thermogravimetry–differential thermogravimetry, differential thermal analysis, differential scanning calorimetry, hot stage microscopy, as well as for the more recent techniques thermogravimetry–mass spectrometry, gas chromatography-time-of-flight-mass spectrometry and isothermal titration calorimetry. In order to evaluate the cyclodextrin complexation capability by thermal methods, we grouped for the first time the guest compound as drugs by anatomical therapeutic chemical classification (ATC), as well as odorants, essential oils and vegetable extracts, antioxidants, fatty acids, oils, fatty acid-based derivatives, other organic, organometallic and inorganic compounds. The formation of cyclodextrin inclusion complexes was emphasized by disappearance of the signal corresponding to the melting or boiling points of the guest compound and the behavior of the hydration water molecules in the complex in comparison with the raw host and guest compounds. The thermal stability of the guest compound after cyclodextrin complexation was also discussed. It was emphasized that thermal methods are some of the most valuable techniques for analyzing cyclodextrin complexes and together with other methods can complete the information related to the host–guest molecular inclusion process and the specific properties of these cyclodextrin complexes.

Validating strategy of quantitative ROESY analysis for structure determination of cyclodextrin inclusion complexes

Highly atom accurate structures of the inclusion complexes between benzydamine hydrochloride (BZY) and β-Cyclodextrin (β-CD) were determined by a method using quantitative ROESY analysis of computational models. Intermolecular contacts were examined in the ROESY spectrum that provided details of the portions of BZY encapsulated in the cavity and the probable mode of entry. Molecular docking studies presented negative binding energies which proved spontaneous complexation between β-CD and BZY and displayed two different modes of binding. Molecular mechanics (MM) studies were performed for both rings, in different orientations and from both cavity ends, to gauge their inclusion depth and mode of entry. Molecular dynamics (MD) studies were carried out to visualise the complexation process. Large number of minimum energy conformations from the MD runs were analysed by comparing their calculated intensities with experimental ROESY cross peak intensities to get the most probable structures of the ensembles.

Identification of β -cyclodextrin inclusion complex by infrared spectroscopy

Fast and reliable identification of obtaining product is very important in the industrial technology of synthesis of pharmaceutical substances.
 Objective - to study inclusion complexes of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with mint oil by applying near infrared spectroscopy absorption. Compare the spectra obtained with the spectra of equimolar mechanical mixture of the respective components.
 Β-cyclodextrin complexes with α-bromizovalerian acid and β-cyclodextrin with mint oil were prepared at a well-known technique. Mechanical mixture of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with mint oil were obtained by mixing the components in a molar ratio of 1:1.
 This paper shows the possibility using method of absorption near-infrared spectroscopy for rapid identification β-cyclodextrin inclusion complexes, as an example used complexes of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with peppermint oil. By comparing the spectra obtained inclusion complexes with the spectra of equimolar mechanical mixture of the corresponding components proved reliability the identification of the target product and the ability to distinguish between an inclusion complex and the mechanical mixture of the components. It is shown that the near infrared spectra obtained using an instrument Thermo Nicolet IS50, Thermo Scientific, inclusion complexes of β-cyclodextrin with a different guest molecules are different from each other.

Encapsulation in cyclodextrins to widen the applications of essential oils

There is a growing interest for aromatic and biological properties of essential oils as alternatives to synthetic chemicals and drugs. However, essential oils and their components are poorly soluble in aqueous systems and are highly sensitive to degradation and evaporation. These drawbacks can be overcome by encapsulation into cyclodextrins, which are non-toxic cyclic oligosaccharides obtained from the enzymatic degradation of starch. Cyclodextrins inclusion complexes offer solutions to many limitations of the use of essential oils in the food, pharmaceutical and cosmetic industries. This article reviews essential oils encapsulation in cyclodextrins. The strength of binding between cyclodextrins and essential oils components covers a wide range of formation constants with values ranging from 13 to 166,338 M−1. The encapsulation in cyclodextrins can increase the aqueous solubility of essential oils up to 16-fold and reduce their photodegradation rates up to 44-fold, while ensuring a gradual release. We also discuss the effect of encapsulation on biological activities, such as antimicrobial and antioxidant properties of essential oils. Finally, we present novel cyclodextrin-based approaches in the sectors of textiles and nanofibres.

Contribution of headspace to the analysis of cyclodextrin inclusion complexes

Headspace technology is a sampling method of a gas, which has been previously in contact with a liquid or a solid matrix from which volatiles were released into the gaseous phase. It is generally coupled to a subsequent gas chromatography analysis. The headspace analysis can be carried out either as a one-step extraction (static or equilibrium headspace) or as a continuous extraction (dynamic headspace). The static headspace gas chromatography (SH-GC) is gaining an increasing interest for the study of cyclodextrin (CD) inclusion complexes with volatile compounds. CDs are natural supermolecular hosts able to encapsulate volatile compounds and improve their functionalities (e.g. solubility, stability, retention, controlled release). Herein, the application of the SH-GC in the CD field will be reviewed. This paper will focus on the characterization of the inclusion complexes via the SH-GC, mainly aiming at the determination of formation constant (Kf) and encapsulation efficiency (EE%) values. Moreover, it will review the application of the SH-GC to monitor the properties of volatile compounds upon encapsulation (e.g. retention, controlled release).

Advances in the use of functional composites of β-cyclodextrin in electrochemical sensors.

β-Cyclodextrin (β-CD) possess a hydrophobic inner cavity and a hydrophilic exterior surface. They exhibit excellent inclusion properties with the guest molecules that match cavity size, and β-CD-based materials drew widespread attention in electrochemical sensors. The hydroxy groups at the edge of the cavity can form hydrogen bonds and undergo electrostatic and dipole-dipole interactions with other molecules. This review (with 109 refs.) reveals β-CD-based detection mechanisms from the viewpoint of the size/shape-fit concept, and summarizes the current state of multiple electrochemical sensors based on the use of β-CD and functionalized β-CD such as carboxymethyl-β-CD, mono-(6-ethanediamine-6-deoxy)-β-CD, hydroxypropyl-β-CD, thio-β-cyclodextrin,and others. Graphical abstract Schematic diagram of cyclodextrin inclusion complex formation in aqueous solution, represents water molecules, represents guest molecule.

Investigation of Solubility Enhancement Approaches of Ticagrelor

ABSTRACT
 Ticagrelor is an orally administered antiplatelet medicine, direct-acting P2Y12-receptor antagonist. Ticagrelor binds reversibly and noncompetitively to the P2Y12 receptor at a site distinct from that of the endogenous agonist adenosine diphosphate (ADP). Inhibition of platelet aggregation stimulated by ADP is a commonly used pharmacodynamic parameter for P2Y12-receptor antagonists.
 Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10?g/mL at room temperature. Ticagrelor exhibits no pKa value within the physiological range. Ticagrelor does not exhibit pH-dependent solubility and is defined as ‘low solubility low permeability’ under the Biopharmaceutics Classification System (Class IV). The mean absolute bioavailability of ticagrelor in healthy volunteers is 36 %
 Nanoparticles preparation and complexation is one of the recently used approaches to enhance the solubility of drugs. The aim of the present work was to improve the solubility and dissolution of ticagrelor by preparing nanoparticles and cyclodextrin inclusion complex of ticagrelor and then incorporated in to tablet dosage form. Fifteen formulas of nanoparticles were prepared by antisolvent precipitation method (solvent displacement method) utilizing one of the three polymers (PVP, Poloxamer, and HPMC) at three different drugs: polymer and solvent: anti-solvent ratios and nine formulas of cyclodextrin inclusion complex with HP?CD by three preparation methods, physical trituration, kneading and solvent evaporation, which increase the solubility and dissolution rate of ticagrelor via formation of inclusion complex with HP?CD.
 The prepared formulas were characterized regarding the saturated solubility, polydispersity index, particle size by nano laser particle size analyzer, % yield, entrapment efficiency, and flowability, FTIR, DSC, and SEM. The selected formulas were prepared as tablets.
 The prepared tablets were evaluated for drug content, weight variation, hardness, and friability. In vitro dissolution data of the prepared tablets were analyzed using similarity factor (f2) and dissolution efficiency (DE). 
 Among all the prepared nanoparticles formulas, formula (F12) which contain HPMC as a polymer at polymer: drug ratio of (1:1) and solvent: antisolvent ratio of (1:1) was considered as the optimum formula which shows good evaluation parameters in addition to the increment in the solubility to about 9 times than that of the pure drug. The nanoparticle of the selected formula (F12) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 88 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively). Moreover, the analysis by DSC and SEM of the nanoparticles of the selected formula (F12) indicate a reduction in the crystallinity and amorphization of the drug. It can be concluded that the selected formula is a promising formula for the preparation of ticagrelor nanoparticles the incorporation in a tablet dosage form.
 Regarding ticagrelor inclusion complex with HP?CD Solvent evaporation method was the most effective method regarding ticagrelor solubilization and optimum formula of inclusion complex (F23) show increment in saturated solubility about ten times that of pure drug.
 The ticagrelor inclusion complex of the selected formula (F23) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 90 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively). 

Bioresorbable antibacterial PCL‐PLA‐nHA composite membranes for oral and maxillofacial defects

Degradable implant membranes designed to separate hard and soft tissues and to trigger the growth of underlying bone and with antimicrobial properties are needed for the management of bone defects, ridge augmentation and to facilitate dental implants. In this study, the composite scaffolds of poly(lactic acid) (PLA), poly(caprolactone) (PCL) blended with nano hydroxyapatite and cefixime‐β cyclodextrin (Cfx‐βCD) inclusion complexes were synthesized by electrospinning. The prepared electrospun fibrous membranes were characterized by scanning electron microscopy and Fourier transform infrared (FTIR) spectroscopy. Membranes were microporous with random fibers in the range of 0.2–0.37 µm. The data from FTIR spectral analysis helped to characterize the presence of PCL, PLA, Cfx, and βCD in the electrospun membranes. In addition, the mechanical properties (i.e., elastic modulus and tensile strength) of the scaffolds were investigated. The mechanical strength and suture retention ability of the membranes was comparable to that of skin grafts. Drug release assays confirmed the slow release of Cfx from the membranes in the presence of βCD and antimicrobial studies showed that the membranes possessed antibacterial properties. The interaction of cells with membranes was evaluated by culturing them with the mouse pre‐osteoblast cell line MC3T3 and assessment of bone formation was done using Alizarin Red Assay. Culturing MC3T3 cells on the scaffolds showed that cells attached and entered the membranes and increased in number over time. In summary, these membranes are flexible, strong, bactericidal and osteogenic, which are the ideal implant properties for dental and maxillofacial surgery. POLYM. COMPOS., 40:1564–1575, 2019. © 2018 Society of Plastics Engineers

Release behavior of allyl sulfide from cyclodextrin inclusion complex of allyl sulfide under different storage conditions

The stability of allyl sulfide, an organosulfur compound present in garlic oil, in its α-, β-, and γ-cyclodextrin inclusion complexes was investigated under various storage conditions. The complexes of cyclodextrins and allyl sulfide were prepared by spray drying. The storage temperature, relative humidity, and initial moisture content of the inclusion complex had different effects on the release rate of allyl sulfide. Allyl sulfide in α-cyclodextrin complexes had a lower release rate than in β- and γ-cyclodextrin complexes at 100°C and at 50°C under 6, 40, 54, and 73% relative humidity. The initial moisture content affected only the release rate of allyl sulfide from α-cyclodextrin complexes. The release behavior of allyl sulfide can be correlated with the first-order release rate equation with a normal Gaussian distribution of free energy of activation of release rate constant. The results indicated α-cyclodextrin is a suitable material for controlled release of allyl sulfide.

Aliphatic Polyester Nanofibers Functionalized with Cyclodextrins and Cyclodextrin-Guest Inclusion Complexes.

The fabrication of nanofibers by electrospinning has gained popularity in the past two decades; however, only in this decade, have polymeric nanofibers been functionalized using cyclodextrins (CDs) or their inclusion complexes (ICs). By combining electrospinning of polymers with free CDs, nanofibers can be fabricated that are capable of capturing small molecules, such as wound odors or environmental toxins in water and air. Likewise, combining polymers with cyclodextrin-inclusion complexes (CD-ICs), has shown promise in enhancing or controlling the delivery of small molecule guests, by minor tweaking in the technique utilized in fabricating these nanofibers, for example, by forming core–shell or multilayered structures and conventional electrospinning, for controlled and rapid delivery, respectively. In addition to small molecule delivery, the thermomechanical properties of the polymers can be significantly improved, as our group has shown recently, by adding non-stoichiometric inclusion complexes to the polymeric nanofibers. We recently reported and thoroughly characterized the fabrication of polypseudorotaxane (PpR) nanofibers without a polymeric carrier. These PpR nanofibers show unusual rheological and thermomechanical properties, even when the coverage of those polymer chains is relatively sparse (~3%). A key advantage of these PpR nanofibers is the presence of relatively stable hydroxyl groups on the outer surface of the nanofibers, which can subsequently be taken advantage of for bioconjugation, making them suitable for biomedical applications. Although the number of studies in this area is limited, initial results suggest significant potential for bone tissue engineering, and with additional bioconjugation in other areas of tissue engineering. In addition, the behaviors and uses of aliphatic polyester nanofibers functionalized with CDs and CD-ICs are briefly described and summarized. Based on these observations, we attempt to draw conclusions for each of these combinations, and the relationships that exist between their presence and the functional behaviors of their nanofibers.

A Review on Solubility Enhancement of Carvedilol—a BCS Class II Drug

Purpose Carvedilol is a third generation non-cardioselective β-blocker used in the treatment of hypertension and demonstrated a potential in the treatment of cardiovascular diseases such as myocardial infarction and arrhythmias. For any drug to be therapeutically effective, it must enter the systemic circulation and to do so, it should have an optimum aqueous solubility at the site of absorption which is a major hurdle to overcome by a formulation scientist. Carvedilol belongs to BCS (biopharmaceutical classification system) class II drugs, thus having low solubility and poor bioavailability (around 25%). Hence, the purpose of this review is to elaborate on several approaches to increase the solubility, dissolution, and bioavailability of carvedilol. Methods Micronization, solid dispersions, cyclodextrin inclusion complex, hydrotropy, nanoformulation which include nanocrystals, nanosuspension, nanoemulsions, dendrimers, and polymeric nanoparticles. It also includes methods that have not been used on carvedilol such as cocrystallization and coamorphous technology. Results Several approaches have successfully increased solubility and bioavailability of carvedilol and several other unexplored methods which have the potential to improve the aqueous solubility of carvedilol but have not been applied till date have also been discussed in the review. Conclusion There are various approaches explored to increase the solubility of carvedilol with every technique having certain advantages and drawbacks. Micronization and nanoformulations (dendrimers, nanoemulsion, nanosuspension, nanocrystals, polymeric nanoparticles) are the most widely used technique for solubility enhancement of carvedilol on laboratory scale due to higher solubility and dissolution rate but they have poor industrial applicability due to difficulty in scale-up and low yield. Efforts are being made to carry out different solubility enhancement techniques with good industrial applicability for carvedilol, e.g., cocrystals. Cocrystals and coamorphous approach for poorly soluble drugs having similar properties to carvedilol have shown good solubility, dissolution, and bioavailability compared to few techniques discussed in this review, and are being widely explored to overcome the drawbacks associated with its method of preparation by carrying out certain advancements (e.g., hot melt extrusion and sonocrystallization) to produce carvedilol cocrystals and coamorphous compound with unique properties in future development.

Characterization and antioxidant activity of the complexes of tertiary butylhydroquinone with β-cyclodextrin and its derivatives

Tertiary butylhydroquinone (TBHQ) is a water-insoluble antioxidant. In this study, three cyclodextrin inclusion complexes were prepared to improve the water solubility of TBHQ and expand its range of application. Analysis of phase solubility indicated that TBHQ can form 1:1 inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and dimethyl-beta-cyclodextrin (DM-β-CD) and 1:2 inclusion complex with beta-cyclodextrin (β-CD). The possible inclusion configuration between TBHQ and CDs was determined through FT-IR, PXRD, DSC, NMR, and SEM analyses. Results were validated by theoretical study of AutoDock molecular docking. The scavenging effects of the inclusion complexes were not effective on DPPH radical but higher on hydroxyl, superoxide and ABTS+ radicals than that of TBHQ monomer. Moreover, the water solubility of TBHQ increased after complexation with HP-β-CD and DM-β-CD. The stability of TBHQ is related to the type of storage materials used, and the stability can be improved by complexation with CDs.

Rutin and Its Cyclodextrin Inclusion Complexes: Physico-chemical Evaluation and in vitro Activity on B164A5 Murine Melanoma Cell Line.

Recent studies have shown that rutin presents a heightened interest due to the plethora of biological activities. The major drawback for this phytocompound is the poor water solubility, a parameter that limits its bioavailability. The study aimed to prepare and assess the inclusion complexes of rutin with β-cyclodextrin (BCD) and hydroxypropyl-β-cyclodextrin (HPBCD), followed by the evaluation of the antioxidant, antiproliferative and pro-apoptotic activity against B164A5 murine melanoma cell line. Inclusion complexes were prepared by kneading method. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction were used in order to assess their formation. Antioxidant activity was determined by DPPH assay. Antiproliferative and pro-apoptotic effects where tested by MTT, respectively Annexin V-PI assays. Physico-chemical methods proved that incorporation took place. Results show that rutin presents antioxidant activity, and complexation increases this property. After 72 h of incubation at the concentration of 100 µM rutin proved to be an active antiproliferative and pro-apoptotic compound against B164A5 cells. Incorporation in BCD and HBCD maintained the activity, thus representing an important finding and open path for in vivo experiments.

Preparation and Characterization of Thalidomide Hyroxy Propyl  -Cyclodextrin Inclusion Complex

Preparation and Characterization of Thalidomide Hyroxy Propyl  -Cyclodextrin Inclusion Complex

Evaluation of Cyclodextrins as Environmentally Friendly Wettability Modifiers for Enhanced Oil Recovery

In the present work, the use of Cyclodextrins (CDs) as wettability modifiers for enhanced oil recovery (EOR) was evaluated. Cyclodextrins (CDs) are cyclic oligosaccharides that form inclusion complexes with various organic molecules, including n-alkanes. Wettability was evaluated through the contact angle (θ) of an n-dodecane drop in contact with a quartz surface and immersed in a 0.6 M NaCl aqueous solution containing the CDs. The quartz surface was functionalized with octadecyltrichlorosilane (OTS), rendering the surface oil-wet (C18-quartz). Here, the n-dodecane, the saline solution and the C18-quartz represent the oil, the reservoir brine and an oil-wet rock surface, respectively. In the absence of CDs, the n-dodecane drops spread well over the C18-quartz, showing that the surface was oleophilic. In the presence of CDs, remarkable effects on the wettability were observed. The most dramatic effects were observed with α-cyclodextrin (α-CD), in which case the C18-quartz surface changed from oil-wet (θ = 162°) in the absence of CD to water-wet (θ = 33°) in the presence of 1.5% (w/v) α-CD. The effects of the CDs can be explained by the formation of surface-active inclusion complexes between the CDs and n-dodecane molecules. The CD inclusion complexes can be regarded as pseudo-surfactants, which are less harmful to the environment than the traditional surfactants employed by the petroleum industry.

Spectroscopic methods for aqueous cyclodextrin inclusion complex binding measurement for 1,4-dioxane, chlorinated co-contaminants, and ozone

Recalcitrant organic contaminants, such as 1,4-dioxane, typically require advanced oxidation process (AOP) oxidants, such as ozone (O3), for their complete mineralization during water treatment. Unfortunately, the use of AOPs can be limited by these oxidants' relatively high reactivities and short half-lives. These drawbacks can be minimized by partial encapsulation of the oxidants within a cyclodextrin cavity to form inclusion complexes. We determined the inclusion complexes of O3 and three common co-contaminants (trichloroethene, 1,1,1-trichloroethane, and 1,4-dioxane) as guest compounds within hydroxypropyl-β-cyclodextrin. Both direct (ultraviolet or UV) and competitive (fluorescence changes with 6-p-toluidine-2-naphthalenesulfonic acid as the probe) methods were used, which gave comparable results for the inclusion constants of these species. Impacts of changing pH and NaCl concentrations were also assessed. Binding constants increased with pH and with ionic strength, which was attributed to variations in guest compound solubility. The results illustrate the versatility of cyclodextrins for inclusion complexation with various types of compounds, binding measurement methods are applicable to a wide range of applications, and have implications for both extraction of contaminants and delivery of reagents for treatment of contaminants in wastewater or contaminated groundwater.

Interfacial effect of cyclodextrin inclusion complex on gas adsorption kinetics of dry water emulsion

Cyclodextrins (CD) solutions were mixed with hydrophobic SiO2 powders to form a dry-cyclodextrin-water (DCD) emulsion, and the effects of CDs with different concentrations and structures on gas adsorption kinetics were investigated, respectively. α-CD was found to enhance effectively both CH4 and CO2 gases adsorption capacity of DCD, while β-CD was generally negative to guest gas adsorption with one exception related to CH4 under lower concentration. Through analyzing dual interfacial effect of gas inclusion, the dominant competition between gas hydration and gas inclusion was speculated as the main reason for the different CD concentration dependence for CH4 and CO2 adsorption kinetics. Furthermore, based on considering the cooperative control of gas diffusion, hydration reaction, inclusion reaction and inclusion sedimentation, a diffusion-reaction-blocking model was suggested to describe the kinetic process. CH4 gases were found to prefer to exist in DCD with free form, while CO2 gases with adsorption form mainly. The selectiveness closely related to guest gas further illustrated the ‘CD concentration quenching’ appearing in CO2 adsorption rather than CH4 adsorption.

Antimicrobial coatings on polyethylene terephthalate based on curcumin/cyclodextrin complex embedded in a multilayer polyelectrolyte architecture.

Bacterial contamination is a growing concern worldwide. The aim of this work was to develop an antimicrobial coating based on curcumin-cyclodextrin inclusion complex and using polyethylene terephthalate (PET) film as a support matrix. After a pre-treatment aimed to provide sufficient electric charge to the PET surface, it was electrostatically coated with repeated multilayers comprising alternately deposited positively-charged poly-l-lysine (PLL) and negatively-charged poly-l-glutamic acid (PLGA) and carboxymethyl-β-cyclodextrin (CMBCD). The coatings had an architecture (PLL-PLGA)6-(PLL-PLGA-PLL-CMBCD)n, with the number of repeated multilayers n varying from 5 to 20. The CMBCD molecules were either covalently cross-linked using carbodiimide crosslinker chemistry or left unbound. The surface morphology, structure and elemental composition of the coatings were analysed by scanning electron microscopy and energy dispersive x-ray spectroscopy. To impart antimicrobial properties to the coatings they were loaded with a natural phenolic compound curcumin forming inclusion complexes with β-cyclodextrin. The non-cross-linked coatings showed bactericidal activity towards Escherichia coli in the dark, and this activity was further enhanced upon illumination with white light. Curcumin was released from the non-cross-linked coatings into an aqueous medium in the form of cyclodextrin inclusion complex. After the cross-linking, the coating lost its dark antimicrobial activity but retained the photodynamic properties. Stabilized cross-linked curcumin-loaded coatings can serve a basis for developing photoactivated antimicrobial surfaces controlling bacterial contamination and spread.

Mechanochemical Preparation of Stable Sub-100 nm γ-Cyclodextrin:Buckminsterfullerene (C60) Nanoparticles by Electrostatic or Steric Stabilization.

Buckminster fullerene (C60 )'s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C60 is by complexation with γ-cyclodextrins. However, the formed complexes are not stable in time as they rapidly aggregate and eventually precipitate due to attractive intermolecular forces, a common problem in inclusion complexes of cyclodextrins. In this study we attempt to overcome the attractive intermolecular forces between the complexes by designing custom γ-cyclodextrin (γCD)-based supramolecular hosts for C60 that inhibit the aggregation found in native γCD-C60 complexes. The approach entails the introduction of either repulsive electrostatic forces or increased steric hindrance to prevent aggregation, thus enhancing the biomedical application potential of C60 . These modifications have led to new sub-100 nm nanostructures that show long-term stability in solution.