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Ethyl vanillin (EVA) is one of the most popular spices in the world, but it is unstable and is prone to lose its aroma. Host–Guest encapsulation by supramolecular hosts can improve stability of fragrance molecules and endow them with excellent heat-controlled release properties to satisfy requirements in food, cosmetic and tobacco, etc. Herein, two acyclic cucurbit[n]urils (ACBs, M1 and M2) inclusion complexes of EVA were prepared. Their binding behaviors were investigated by 1H NMR, SEM, XRD, FT-IR and TGA. The stoichiometric ratio was 1:1 by Job’s plot and the binding constant was determined by fluorescence titration. The intermolecular interaction between host and guest was studied by 2D-ROESY NMR and the inclusion mode was proposed. Finally, the heat-controlled release experiment indicated that the inclusion complexes of ACBs/EVA possess less volatilization at higher temperature, longer retention time and heat-controlled release. This study provides theoretical and technical guidance for expanding the application of EVA.

Precise delivery of hydrophobic drugs has always been a great challenge for drug delivery systems. To overcome this problem, we designed and synthesized a novel supramolecular host biotin-acyclic cucurbituril (ACBB) at the first time, and we have developed a host-guest amphiphilic complex based on ACBB and amantadine-conjugated cannabinoids (AD-CBD) that self-assembles to form functionalized supramolecular micelles (FSMs) for cell-targeted drug delivery. The 1:1 stoichiometric ratio of the amphiphilic complex and its possible host-guest inclusion behaviors are obtained by fluorescence titration, nuclear magnetic resonance (NMR), Fourier transform-infrared spectroscopy (FT-IR) and thermal analysis (TGA and DSC). Using transmission electron microscope (TEM) and dynamic light scattering (DLS), we have observed that the shape of FSMs was spherical and size was 137-192 nm. In addition, MTT test results show that FSMs have good antitumor activity, taking MCF-7 as an example, the in vitro half-maximal inhibitory concentration (IC

Encapsulation of platinum-based anticancer drugs inside cucurbit[n]urils provides a steric hindrance to drug degradation. This study describes an alternative strategy for the enhancement of in vitro antitumor activity of nedaplatin (NDP) by encapsulating it in the cavity of cucurbit[7]uril (CB[7]). The complexation stoichiometry, binding affinity and geometry were studied via reliable spectroscopic and physicochemical techniques. The stoichiometry of the inclusion complex was 1:1 and the stability constant (KS) value was found to be (2.89 ± 0.26) × 106 M−1 at 293 K, which suggested a favorable inclusion complexation system has been formed. In vitro cytotoxicity of the free NDP and complexed NDP (NDP@CB[7]) was examined by MTT assay using three human cancer cell lines: A549, HCT116, MCF-7. Interestingly, more cytotoxicity on MCF-7 was observed for NDP@CB[7] as compared with free drugs. In addition, NDP@CB[7] showed significantly improved cytotoxicity against A549 and HCT116 cells with up to almost threefold and twofold higher cytotoxicity than that of free NDP, indicating that the encapsulation of NDP in CB[7] can enhance the cytotoxicity of NDP in tested cancer cell lines. The formed species are shown to be stabilized in solution and the host–guest complexation between NDP and CB[7] may allow this strategy to be effective for potential use in drug delivery.

Herein, three pairs of cationic cyclometallated palladium (II) complexes with different types of C^N ligands, which is non-phosphorescent in aqueous solution, interestingly, they can be utilized as turn-on blue phosphorescent probes selectively for ClO

Cannabidiol (CBD) is one specific kind of the cannabinoid in Cannabis sativa L with a wide range of pharmacological activities. However, the poor water solubility and specificity of CBD limits its application in pharmaceutical field. For solving these problems, in this work, we successfully prepared a targeted carrier by grafting biotin (BIO) onto ethylenediamine-β-Cyclodextrin (EN-CD) in a single step to generate a functionalized supramolecule, named BIO-CD. Subsequently, an amantadine-conjugated cannabinoids (AD-CBD) was prepared and self-assembled with the BIO-CD. A series of methods were used to characterize the inclusion behavior and physicochemical properties of AD-CBD and BIO-CD. The results showed that AD-CBD entered the cavity of BIO-CD and formed a 1:1 host-guest inclusion complex. MTT assay and confocal laser scanning microscopy (CLSM) revealed that the targeting effect and anticancer activity of AD-CBD/BIO-CD inclusion complex against three human cancer cell lines were higher than BIO-CD, AD-CBD and free CBD. Moreover, the inclusion complex could release drugs under weakly acidic conditions. These results demonstrated that AD-CBD/BIO-CD inclusion complex possess excellent targeted and anticancer activity, which is hopeful to be applied in clinic as a new therapeutic approach.

This paper reports host-guest inclusion systems of mangiferin (MGF) with four polyamine-modified β-cyclodextrins (PAβCDs). The inclusion complexes have been characterized by 1D and 2D nuclear magnetic resonance (NMR), thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The results show that MGF was encapsulated into the cavities of PAβCDs to form four complexes with 1:1 stoichiometry. The water solubility of the complexes was enhanced markedly, and the cytotoxicity of these complexes to normal cell line HEK293 was significantly reduced in comparison with native MGF. This satisfactory water solubilization and improvement of cytotoxicity with MGF/PAβCDs complexes will be potentially useful for its application as herbal medicine or healthcare products.

Stimuli-responsive drug delivery systems may provide an effective way to treat cancer as they can release cargoes regularly according to changes in the human microenvironment. In this work, we design and prepare acid-controlled release complexes of camptothecin with three pH-sensitive acyclic cucurbit[n]urils. The inclusion complexes have been characterized by 1H and 2D nuclear magnetic resonance, X-ray powder diffraction, and phase solubility diagram. Cells incubated with complexes have been analyzed by high-content analysis, and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of CPT for clinical application.

The design and construction of tumor-targeted drug delivery systems provide us a facile method to treat cancers selectively. In this work, a biotin-targeting inclusion complex based on β-cyclodextrin and methotrexate was designed and prepared successfully. Compared with other delivery systems, in addition to hypotoxicity and high bioavailability, this targeting inclusion complex also has relatively high drug conjugation rate and with the linkage of more than 1/5 targeting ligand. In order to verify physical and chemical properties of this system, a series of experiments were carried out. The results showed that methotrexate-cyclodextrin conjugate could form very stable inclusion complex with biotin-adamantine conjugate. Water solubility of methotrexate was improved greatly by the introduction of β-cyclodextrin. In addition, according to MTT assay results, anticancer activity of amantadine-biotin/methotrexate-cyclodextrin inclusion complex against three human cancer cell lines was higher than methotrexate-cyclodextrin conjugate and free methotrexate. Further, targeting effect of the inclusion complex was also confirmed by the addition of biotin with different concentrations to make biotin receptors be saturated to vary degrees previously, which also provides a strategy for the verification of tumor-targeting of biotin. Serum stability test and drug release test also confirmed that this biotin-targeting inclusion complex was expected to be applied in the field of biomedicine for further research.

The thermal stability and slow release of nicotine are crucial to its shelf-life and applications. In this article, three kinds of acyclic cucurbit[n]urils (ACBs) were synthesized with cation or anion arms, benzene or naphthalene wall, aiming to handily adjust the binding ability of ACBs. The complexation behaviors and binding affinity of nicotine with ACBs in aqueous and solid state were investigated via fluorescence spectroscopy, NMR, XRD, FT−IR and DSC, which revealed the formation of host−guest inclusion systems with different stability constants (Ks). The heat-controlled release in solid state of the complexes were studied via 1H NMR spectra and TGA. Compared to nicotine, the complexes exhibited less volatility, longer retention time, better water solubility and heat-controlled release. It is our special interest to explore the binding behaviors of all kinds of ACBs with nicotine, controlled heat releases of nicotine with ACBs, which will provide a useful approach to achieve novel formulation of nicotine inclusion complexes used for products including nicotine with controlled heat releases.

Supramolecular encapsulation, which removes harmful substances from organisms, has evolved into a new strategy. In this paper, three supramolecular complexes of acyclic cucurbit[n]urils (ACBs) with uric acid (UA) were prepared, and the inclusion behavior of ACBs and UA was studied by fluorescence spectroscopy, UV–vis spectroscopy and nuclear magnetic resonance. Furthermore, the effect of the complexes of UA with ACBs on the expression of inflammatory biomarkers in human hepatoma HepG2 cell lines was characterized through C-reactive protein (CRP) western blot. The results showed UA molecules can be recognized by three ACBs with different binding constants, and ACBs successfully blocked the inflammatory stimulation of UA on HepG2 cell lines and inhibited the expression of the major inflammatory factor CRP by the formation of complexes between UA and ACBs. This article proves that ACBs can efficiently reverse the cytotoxicity of UA, which provides a new method for treating hyperuricemia disease.

The poor water-solubility of Cannabidiol (CBD) seriously hinders its pharmacological activities such as anti-anxiety, anti-epilepsy, anti-oxidation and anti-cancer, etc. In this paper, we successfully designed and synthesized two bridged cyclodextrins (CDs) dimers with different length of bridged chains (succinic acid (SACDD) and 3,3′-thiodipropionic acid (TPACDD)) to encapsulate CBD, a reported DMCD (2,6-Di-O-methyl-β-cyclodextrin) with single cavity was used as a control complex. Their characteristics and inclusion complexation behaviors were investigated via XRD, SEM, NMR and TGA, the obtained data suggests CBD is successfully encapsulated into two cavity of bridged CD dimers with stronger stability constants, compared with DMCD. Water solubility of CBD is significantly promoted by 6.76 × 105 and 4.52 × 105 folds after formation of inclusion complexes, as well as the antioxidant activity in vitro (5.26-fold enhanced). MTT assays shows they remained effective anti-tumor activity, while they barely show cytotoxicity to normal cell. Our work might provide a strategy for development and application of water-solubility CBD.

Ursolic acid (UA) is a pentacyclic triterpenoid of naturally abundance with a broad spectrum of important biological activities and low toxicity. However, potential applications in pharmaceutical industry are severely hampered by its poor water solubility, which leads to low bioavailability. Herein, we harness the unique and superior inclusion capability of a series of amino-appended beta-cyclodextrins (ACDs) to prepare solid inclusion complexes of UA/ACDs. These inclusion complexes were characterized in their solid state by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric (TG) and powder X-ray diffraction (XRD) analyses. Furthermore, their supramolecular binding behavior in aqueous solution was investigated by one-dimensional (1D)- and two-dimensional (2D)-nuclear magnetic resonance (NMR) spectroscopic experiments and NMR-based phase solubility analysis. Binding stability constants (Ks) were determined (1799, 1410, 889 and 993 L mol(-1) for UA/a0, UA/a1, UA/a2 and UA/a3, respectively), and dynamic bimodal inclusion modes with a 1:1 inclusion stoichiometry for UA/ ACDs systems were proposed. Water solubility of UA is dramatically promoted by more than 200-fold after formation of inclusion complexes. In vitro cytotoxicity of UA achieves significant elevation against human cancer cell lines HepG2, HT-29 and HCT116 by inclusion complexation from MIT assay, while these inclusion complexes show no cytotoxicity against human normal cell line LO2, which confirms their safety. These results would benefit to the further development of liquid formulation of UA for pharmaceutical uses. (C) 2019 Elsevier B.V. All rights reserved.

The purpose of this study was to develop a novel folate-modified host-guest complex to enhance antitumor activity of the artesunate and improve the solubility and stability by encapsulated in β-cyclodextrin and linked with folate. In this work, we designed and prepared the inclusion complex of adamantanamine conjugated artesunate (AD-ATS) with folic acid-ethylenediamine-β-cyclodextrin (FA-EN-β-CD). This material was characterized by 1D and 2D NMR, XRD, TG and SEM. The results suggested that AD-ATS was encapsulated within the FA-EN-β-CD cavity to form host-guest inclusion complex, and the water solubility of AD-ATS was improved in the form of inclusion complex with FA-EN-β-CD. The assessment of antitumor activity showed that cytotoxicity of AD-ATS/FA-EN-β-CD complex was significantly enhanced in comparison to free AD-ATS, ATS/β-CD inclusion complex and ATS/FA-EN-β-CD inclusion complex.

The inclusion complexation behaviors of glycyrrhetic acid (CTA) with four polyamine-modified β-cyclodextrins (CDs) have been investigated by 1 H and 2D NMR, thermal gravimetric analysis, X-ray power diffraction and scanning electron microscopy. The results showed that Glycyrrhetic acid was encapsulated into the cavity of cyclodextrin to form the complexes with 1:1 stoichiometry. The water solubility of GTA was significantly enhanced by inclusion complexation with polyamine-modified β-cyclodextrins. The calculated IC 50 values indicated that the antitumor activities of inclusion complexes were better than that of GTA. Satisfactory aqueous solubility, along with high thermal stability of inclusion complexes will be potentially useful for their application on the formulation design of natural medicine.

Since the antitumor activity of cisplatin was discovered in 1967 by Rosenberg, platinum-based anticancer drugs have played an important role in chemotherapy in clinic. Nevertheless, platinum anticancer drugs also have caused severe side effects and cross drug resistance which limited their applications. Therefore, a significant amount of efforts have been devoted to developing new platinum-based anticancer agents with equal or higher antitumor activity but lower toxicity. Until now, a large number of platinum-based complexes have been prepared and extensively investigated in vitro and in vivo. Among them, some platinum-based complexes revealing excellent anticancer activity showed the potential to be developed as novel type of anticancer agents. In this account, we present such platinum-based anticancer complexes which owning various types of ligands, such as, amine carrier ligands, leaving groups, reactive molecule, steric hindrance groups, non-covalently binding platinum (II) complexes, Platinum(IV) complexes and polynuclear platinum complexes. Overall, platinum-based anticancer complexes reported recently years upon modern structure are emphasized.

To improve the water solubility of daidzein, solid inclusion complexes of daidzein with two amino-modified β-cyclodextrins (ACDs), i.e., mono-6-amino-6-deoxy-β-cyclodextrin (NCD) and mono-6-ethylenediamino-6-deoxy-β-cyclodextrin (ENCD), were prepared by the saturated solution method in water with yields of 83% and 67%, respectively, under the optimized conditions including the ratio of daidzein/ACD of 3:1 and the stirring time of 72 h. The formation of the two inclusion complexes was confirmed by X-ray diffractometry (XRD) and thermo gravimetric (TG) analysis. The inclusion stoichiometry of the inclusion complexes was 1:1 from the Job plot and their complexation stability constants (KS) were 899.2 and 203.8 M−1 from fluorescence titration, respectively. After formation of inclusion complexes with NCD and ENCD, the water solubility of daidzein was dramatically raised to 15.2 and 13.2 mg mL−1 at 25 °C, increasing by 1800 and 1500-fold compared to native daidzein (8.31 μg mL−1).

Solid inclusion complexes between chrysin and four amino-appended β-cyclodextrins (ACDs) were prepared by suspension method and characterized in solid and solution states by kinds of analytical methods. The scanning electron microscopy (SEM) showed distinct micro-morphologies of them. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis revealed their unique thermal properties, such as decomposition temperatures and endothermic points. Powder X-ray diffractometry (XRD) analysis disclosed their unique crystal patterns. Their nuclear magnetic resonance (NMR) analyses provided the variations of chemical shifts before and after the formation of inclusion complexes. Their binding stability constants (Ks) were 574, 842, 704, and 474 L·mol−1, respectively, as determined by spectral titration. A 1:1 inclusion mode with self-assembly of their amino side chains inside the ACD cavity was proposed based on Job plot and 2D-ROESY experiments. Water solubility of chrysin was promoted up to 4411.98 μg·mL−1 after formation of inclusion complexes with ACDs, better than that of β-CD and its derivatives, i.e., HP- and SBE-β-CD. In vitro antioxidant activity of chrysin was also improved after inclusion complexation by the DPPH scavenging assay. Furthermore, in vitro cytotoxicity of solid inclusion complexes towards three human cancer cell lines, A549, HT-29 and HCT116 were enhanced significantly.

An effective tumor targeting drug delivery systems was designed and synthesized by conjugating pH-sensitive maleamide derivatives to Mono-(6-deoxy-6-amino)-β-CD. Their characteristics and inclusion behaviors with insoluble anticancer drug PPT were investigated in both solution and solid state by means of 1H NMR and 2D-ROESY, XRD, DSC and SEM, which reveal PPT is successfully encapsulated in the cavity of CD derivatives with different stability constants (Ks). Water solubility of PPT are significantly increased to 60.35 and 22.89 mg·mL−1 after formation of inclusion complexes with host-1 and host-2, compared with free PPT (0.12 mg·mL−1). Their acid-controlled release has been studied in vitro by 1H NMR and UV-Vis spectra, living cells incubated with host 1-2 were observed by Inverted fluorescence microscope to confirm pH-response releasing. Moreover, host-1/PPT and host-2/PPT maintain effective cell proliferation inhibition to human cancer, while their cytotoxicity to normal cell is significantly reduced. Our work shows inspiring potential in tumor-targeted delivery and acid-controlled release of PPT both in vitro.

Daidzein is an isoflavone of naturally abundance existing in plants and foods which has attracted much attention for its significant benefits on human health. However, its application was severely limited by its poor solubilities, instability and low bioavailability. To overcome these drawbacks, inclusion complexes of daidzein with two cyclodextrin (CD) derivatives, i.e., 2-hydropropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) were prepared and characterized both in solution and solid state by 1D and 2D NMR, XRD, SEM and elemental analyses. Fluorescence spectroscopy and the Job plot were used to demonstrate a mainly 1:1 inclusion mode between daidzein and CDs. Their thermal stabilities were evaluated with TG and DSC experiments. Moreover, water solubility of daidzein was significantly improved by inclusion complexation with CDs. These results might suggest valuable approaches to developments of new pharmaceutical formulations of daidzein.

In this study, the one-pot three-component synthesis of 2-amino-4H-chromenes was accomplished by supramolecular catalysis using a series of well-designed amino-appended β-cyclodextrins (ACDs) in water. The catalytic mechanism was elucidated in detail with 1D and 2D NMR and ESI-MS analyses, while the key roles of amino side chains of ACDs in the reaction chemoselectivity were addressed for the first time.

Well-designed amino-appended β-cyclodextrins (ACDs) with an amino side chain of different lengths at the primary face of β-CD were synthesized and employed in the catalytic synthesis of a series of tetraketones as supramolecular catalysts in water for the first time. Yields of 58–97% were obtained with up to 30 examples of substrate. The catalyst could be recycled easily, while a 92% yield and 84% rate of catalyst recovery could be achieved after 8 cycles of catalyst recycling. Moreover, a catalytic mechanism merging supramolecular catalysis and aminocatalysis could be proposed through detailed 1D and 2D NMR, ESI-MS and Job plot analyses. This protocol retained the promising characteristics of ambient temperature, green medium, simple operation, broad substrate scope, excellent yields, superb catalyst recycling performance and unique catalytic mechanism.

A practical and economical five-step synthesis of the flavone scutellarein has been achieved in 60% overall yield using the available and cheap 2,6-dimethoxy-1,4-benzoquinone as starting material. The reaction sequence involved reduction to the corresponding quinol, Friedel-Crafts acetylation, Claisen-Schmidt condensation with p-methoxybenzaldehyde, cyclisation and demethylation. The procedure is operationally simple and amenable to scale-up synthesis.

Classical platinum(II) anticancer agents are widely-used chemotherapeutic drugs in the clinic against a range of cancers. However, severe systemic toxicity and drug resistance have become the main obstacles which limit their application and effectiveness. Because divalent cisplatin analogues are easily destroyed in vivo, their bioavailability is low and no selective to tumor tissues. The platinum(IV) prodrugs are attractive compounds for cancer treatment because they have great advantages, e.g., higher stability in biological media, aqueous solubility and no cross-resistance with cisplatin, which may become the next generation of platinum anticancer drugs. In addition, platinum(IV) drugs could be taken orally, which could be more acceptable to cancer patients, breaking the current situation that platinum(II) drugs can only be given by injection. The coupling of platinum(IV) complexes with tumor targeting groups avoids the disadvantages such as instability in blood, irreversible binding to plasma proteins, rapid renal clearance, and non-specific distribution in normal tissues. Because of the above advantages, the combination of platinum complexes and tumor targeting groups has become the hottest field in the research and development of new platinum drugs. These approaches can be roughly categorized into two groups: active and passive targeted strategies. This review concentrates on various targeting and delivery strategies for platinum(IV) complexes to improve the efficacy and reduce the side effects of platinum-based anticancer drugs. We have made a summary of the related articles on platinum(IV) targeted delivery in recent years. We believe the results of the studies described in this review will provide new ideas and strategies for the development of platinum drugs.

The targeted or responsive systems are appealing therapeutic platforms for the development of next-generation precision medications. So, we design and prepare acid-controlled release complexes of podophyllotoxin (POD) and etoposide (VP-16) with pH-labile acyclic cucurbit[n]urils, and their characteristics and inclusion complexation behaviors were investigated via fluorescence spectroscopy, nuclear magnetic resonance and X-ray power diffraction. Cells incubated with complexes have been analyzed by high-content analysis (HCA), and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of POD and VP-16 for clinical application.

The targeted or responsive systems are appealing therapeutic platforms for the development of next-generation precision medications. In this article the first experimental and theoretical investigation of the complexation between podophyllotoxin (POD) and three β-cyclodextrin (β-CD) derivatives (NH2-β-CD, SA-β-CD and Bridged β-CD) are presented. The inclusion complexes are characterized by 1H and 2D nuclear magnetic resonance (NMR), thermal gravimetric analysis (TGA), and X-ray powder diffraction (XRD). Cytotoxicity tests are furnished by MTT assay. The results show that POD is encapsulated in the cavity of β-CD derivatives to form inclusion complexes with different stability constants (Ks). The cytotoxicity of these inclusion complexes against normal human kidney cell line 293 T is significantly reduced, while the inclusion complexes of SA-β-CD/POD and Bridged-β-CD/POD exhibit the same cytotoxicity against cancerous cell lines HCT116, HepG2 and SY5Y in comparison with native POD. Moreover, the stability constants of the inclusion complexes can affect their cytotoxicity, which provides a strategy for low cytotoxicity systems of POD for clinical application.

Cyclodextrins, one of safe excipients, are able to form host-guest complexes with fitted molecules given the unique nature imparted by their structure in result of a number of pharmaceutical applications. On the other hand, targeted or responsive materials are appealing therapeutic platforms for the development of next-generation precision medications. Meanwhile, cyclodextrin-based polymers or assemblies can condense DNA and RNA in result to be used as genetic therapeutic agents. Armed with a better understanding of various pharmaceutical mechanisms, especially for cancer treatment, researchers have made lots of works about cyclodextrin-based drug delivery systems in materials chemistry and pharmaceutical science. This Review highlights recent advances in cyclodextrin-based delivery systems for cancer treatment capable of targeting or responding to the physiological environment. Key design principles, challenges and future directions, including clinical translation, of cyclodextrin-based delivery systems are also discussed.

A series of novel artesunate-polyrotaxanes (ATS-PRs) with folic acid capped, in which artesunate (ATS) was covalently bound to a cyclodextrin (CD) of the polyrotaxane (PR), were synthesized and were characterized by NMR, XRD, TG and DSC. The cytotoxicities of ATS-PRs on human colon cancer cell lines HT-29, SW480, HTC116 and DLD-1 showed that their antitumor activities were better than that of artesunate (ATS) and dihydroartemisinin (DHA). These ATS-PRs may provide a useful approach to the development of a highly effective drug candidate for the chemotherapy of human colon cancer.

The efficient tumor targeting drug carrier was designed by bioconjugation of folic acid to β-cyclodextrin through a polyamine cationic spacer. The characterization and inclusion complexation behavior of the inclusion complex of hydrophobic drug scutellarin with folic acid-polyamine-β-cyclodextrin were investigated in both solution and solid state by means of phase-solubility, nuclear magnetic resonance, X-ray power diffraction, thermal gravimetric analysis, and scanning electron microscopy. Besides, the solubilization efficiency and antitumor activity of the inclusion complex were tested by saturated solution and MTT (Thiazole blue) method. Solubility and antitumor activity studies showed higher solubilizing ability and antitumor activity of the inclusion complex in comparison to free scutellarin. The folic acid-polyamine-β-cyclodextrin that is presented may be promising active tumor-targeting carrier candidates via folate mediation. Copyright © 2015 John Wiley & Sons, Ltd.

Tetrahydro-4H-chromenes were synthesized via a one-pot three-component condensation catalyzed by β-cyclodextrin (β-CD) under mild conditions in water. The supramolecular reaction mechanism was extensively elucidated by spectroscopic analyses. This protocol could provide a unique strategy for the preparation of such biologically important scaffolds in a supramolecular-catalyzed mode.

Soluble poly(ε-lysine)s bearing β-cyclodextrin (β-CD) moieties were prepared by three amino β-CD derivatives and N-succinylated poly(ε-lysine), in which the poly(ε-lysine) and amino β-CD derivatives were bonded covalently to the end carboxyl groups of succinic acid by peptide bonds. 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) and N-hydroxysuccinimide (NHS) were chosen to assist the reaction. The three poly(ε-lysine) derivatives were characterized by 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FT-IR). The synthesis process is simple, feasible and has strong practicability. The target polymers can serve as new polymer biomaterial for use in the biotechnology area.

The inclusion complexation behavior of scutellarein (SCUE) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has been investigated in both solution and in the solid state. SCUE/HP-β-CD solid system was prepared by suspension method. The formation of SCUE/HP-β-CD complex in aqueous solution was demonstrated by fluorescence spectroscopy, and the Job plot showed a maximum at a molar fraction of 0.5, indicating 1:1 inclusion complexation between SCUE and HP-β-CD. However, SCUE/HP-β-CD inclusion complex was characterized by means of XRD, DSC, (1)H, and two-dimensional NMR. Through the complexation between HP-β-CD and SCUE, the water solubility and antitumor activity of SCUE were obviously increased. This satisfactory water solubility and high antitumor activity of the SCUE/HP-β-CD complex will be potentially useful for its application on human colon cancer chemotherapies.

Two novel syntheses of the flavone luteolin are described. In the first, 3,5-dimethoxyphenol was converted to 2-hydroxy-4,6-dimethoxyacetophenone and then by condensation with 3,4-dimethoxybenzaldehyde to 2′-hydroxy-3,4,4′,6′-tetramethoxychalcone. In the second, the chalcone step was prepared in which 3,5-dimethoxyphenol was acylated with 3,4-dimethoxycinnamoyl chloride. The chalcone was then cyclised with iodine and demethylated with pyridine hydrochloride to form luteolin in 47% and 40% overall yield, respectively. Several disadvantages of previous syntheses like long reaction time, harsh reaction conditions and low overall yield have been overcome.

Two routes for the synthesis of the flavanone naringenin are described. In the first, 3,5-dimethoxyphenol is converted to 2-hydroxy-4,6-dimethoxyacetophenone and then by condensation with anisaldehyde to 2′-hydroxy-4,4′,6′-trimethoxychalcone. The chalcone is then cyclised with aqueous hydrochloric acid and demethylated with pyridine hydrochloride to form naringenin in 45% overall yield. The condensation of 2-hydroxy-4,6-dimethoxyacetophenone with anisaldehyde could also directly produce 4′,5,7-trimethoxyflavanone, which was then converted into naringenin in 60% overall yield. In the second route, a single step for the preparation of the chalcone is used in which 1,3,5-trimethoxybenzene is acylated with p-methoxycinnamic acid. Although the synthesis of naringenin is achieved in a lower overall yield of 29%, the process is simpler.

Two routes for the synthesis of the flavone apigenin are described. In the first, taxicatigenin was converted to 2-hydroxy-4,6-dimethoxyacetophenone and then by condensation with anisaldehyde to 2′-hydroxy-4,4′,6′-trimethoxychalcone. The latter was cyclised with iodine and demethylated with pyridine hydrochloride to form apigenin in 53% overall yield. In the second route, a single step for the preparation of the chalcone was used in which 1,3,5-trimethoxybenzene was acylated with p-methoxycinnamic acid. Although the synthesis of apigenin was achieved in a lower overall yield of 34%, the process was simpler.

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of dihydroartemisinin with β-cyclodextrin and its derivatives, sulfobutyl ether β-cyclodextrin (SBE-β-CD), mono[6-(2-aminoethylamino)-6-deoxy]-β-cyclodextrin (en-β-CD) and mono{6-[2-(2-aminoethylamino)ethylamino]-6-deoxy}-β-cyclodextrin (dien-β-CD), were studied using phenolphthalein as a spectral probe. Spectral titration was performed in aqueous buffer solution (pH ca. 10.5) at 25 °C to determine the binding constants. The inclusion complexation behaviors were investigated in both solution and solid state by means of NMR, TG, XRD. The results showed that the water solubility and thermal stability of dihydroartemisinin were significantly increased in the inclusion complex with cyclodextrins (CDs). According to 1H NMR and 2D NMR spectroscopy (ROESY), the A, B rings of dihydroartemisinin can be included into the cavity of CDs. The enhanced binding ability of CDs towards dihydroartemisinin was discussed from the viewpoint of the size/shape-fit concept and multiple recognition mechanism between host and guest.

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of mangiferin (MGF) with β-cyclodextrin and its derivatives (hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and mono (6-ethylene-diamino-6-deoxy)-β-cyclodextrin (ENβCD)) were investigated in both solution and solid state by means of PL spectroscopy, (1)H and 2D NMR, XRD, TG and DSC. The results showed that the water solubility and thermal stability of MGF were significantly increased in the inclusion complex with cyclodextrins. The MGF/CDs complexes will be potentially useful for the design of a novel formulation of mangiferin for herbal medicine.

Cyclodextrin-based supermolecular systems have become one of significant nonviral gene delivery carriers. In this study, epsilon-polylysine-grafted-succinic acid-grafted-β-cyclodextrin-LMW PEI (PPC) and adamantane-functionalized poly-(ethylene glycol) derivative (PEG-AD) were synthesized, and PEG-AD was encapsulated into PPC to form the complexes. These complexes were used to condense pDNA to make polyplexes, which biophysical properties, cytotoxicity and transfection efficiencies were studied. The results showed that the polyplexes were less cytotoxic than branched PEI without degrading the transfection efficiency. These findings suggest that the complexes with high stability could be an effective and low-toxicity carrier for delivering nucleic acid to target cells.

We report the preparation of inclusion complexes between rhein and four polyamine-modified β-cyclodextrins, namely amino-β-cyclodextrins (NH2-βCD), ethylenediamine-β-cyclodextrins (EN-βCD), diethylenetriamine-β-cyclodextrins (DETA-βCD) and triethylenetetramine-β-cyclodextrins (TETA-βCD) using suspension method. The solution and solid state forms of the inclusion complexes of rhein with polyamine-β-cyclodextrins were characterized by multiple techniques. Additionally, saturated solution and MTT methods were implemented to assess the water solubilization and in vitro cytotoxicity of the inclusion complexes, respectively. The results suggested that rhein was encapsulated within the CD cavity to form a 1:1 host-guest inclusion complex. Notably, a significant enhancement of the water solubility and in vitro cytotoxicity of rhein was found in the form of inclusion complex with polyamine-β-cyclodextrin.

As a prerequisite of gene delivery in living cells, DNA condensation has attracted more and more attention. In order to improve the efficiencies of polyamine-β-cyclodextrin-based cationic polyrotaxanes (PR-EDA and PR-DETA) as DNA condensation materials, we have designed and prepared two novel scutellarin-grafted cationic polyrotaxanes (PR-EDA-SCU and PR-DETA-SCU), in which scutellarins (SCU), the planar molecules, were conjugated on the cyclodextrin molecules of PR-EDA and PR-DETA. These materials were characterized by 1D and 2D NMR, XRD, TG and DSC. The electrophoresis assays showed that pDNA condensation efficiencies of PR-EDA and PR-DETA were better than that of PR-EDA and PR-DETA. The complexes of PR-EDA, PR-DETA, PR-EDA-SCU and PR-DETA-SCU with pDNA were further investigated by zeta potential and atomic force microscopy analysis. The results indicated that the planar structure of SCU played an important role in improvement of pDNA condensation efficiencies of PR-EDA-SCU and PR-DETA-SCU. The satisfactory pDNA condensation abilities of PR-EDA-SCU and PR-DETA-SCU could be helpful in designing non-viral gene delivery vectors to control gene expression and delivery.

Oleanolic acid (OA) is a pentacyclic triterpenoid acid of natural abundance in plants which possesses important biological activities. However, its medicinal applications were severely impeded by the poor water solubility and resultant low bioavailability and potency. In this work, studies on solid inclusion complexes of OA with a series of amino-appended β-cyclodextrins (ACDs) were conducted in order to address this issue. These complexes were prepared by suspension method and were well characterized by NMR, SEM, XRD, TG, DSC and Zeta potential measurement. The 2:1 inclusion mode of ACDs/OA complexes was elucidated by elaborate 2D NMR (ROESY). Besides, water solubility of OA was dramatically promoted by inclusion complexation with ACDs. Moreover, in vitro anticancer activities of OA against human cancer cell lines HepG2, HT29 and HCT116 were significantly enhanced after formation of inclusion complexes, while the apoptotic response results indicated their induction of apoptosis of cancer cells. This could provide a novel approach to development of novel pharmaceutical formulations of OA.