Supramolecular Modulation of Antibacterial Activity of Ambroxol by Cucurbit[7]uril.

Supramolecular encapsulation by cucurbit[7]uril (CB[7]) was recently demonstrated to provide a simple and efficient method for antibacterial activity regulation of antibiotics. In this work, CB[7] was shown to form binary host-guest complex with ambroxol hydrochloride (ABX), a clinical mucokinetic and expectorant drug, which was reported to exhibit certain antibacterial activity. 1 H NMR titration and isothermal titration calorimetry experiment results suggested that the 4-hydroxyl cyclohexylamine group of ABX was included inside the CB[7] cavity, with a binding constant Ka of (6.69±0.11)×105  M-1 in phosphate buffered saline (PBS) solution, thermodynamically driven by both enthalpy change (ΔH=-12.2 kJ/mol) and entropy change (TΔS=21.1 kJ/mol). More importantly, ABX's inhibitory activity (MIC50 ) against bacillary strains towards Pseudomonas aeruginosa and Escherichia coli strains was decreased from (5.11±0.31)×10-6  M-1 and (2.63±0.34)×10-5  M-1 to zero upon encapsulation by CB[7], and was subsequently recovered to almost its original activity when a competitive guest, amantadine hydrochloride, for disassembling CB[7]-ABX complex, was added, suggesting that the antibacterial activity of ABX could be readily "turned off/on" upon its complexation and decomplexation with CB[7].

Biomedical applications of Aloe vera.

Over the last centuries, Aloe vera, a plant species belonging to the genus Aloe, have been extensively studied for various therapeutic activities, including anti-bacterial, anti-viral, anti-cancer activity, as well as immunoregulative and hepatoprotective properties, although some of these claimed efficacies are controversial as demonstrated by some of the recent studies. In spite of the intensive historic and recent use of this herb and its extracts in various areas, a well-balanced, systematic review seems crucial in order to gain in-depth comprehensive knowledge about this plant and to reflect and revive the use of Aloe vera in biomedical sciences. This review will focus on summarization of the pharmacological activities and clinical studies of Aloe and various extracts, as well as its extensive application in food chemistry, and will also discuss the future prospects of biomedical applications of this herb.

Inhibition of drug-induced seizure development in both zebrafish and mouse models by a synthetic nanoreceptor.

A synthetic nanoreceptor, cucurbit[7]uril (CB[7]), fully encapsulated pentylenetetrazol (PTZ), a seizure-inducing model drug. As a consequence of the encapsulation, the development of PTZ induced convulsion behaviors in both larval zebrafish and mouse models were dramatically alleviated, suggesting that CB[7] holds great neuroprotection potential against neurotoxic drugs for clinical applications.

Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy.

Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ. HPLC-UV test on the solubility of BDQ in the absence and in the presence of increasing concentrations of CB[7] suggested a host-dependent guest-solubility enhancements. Cardiovascular studies using an in vivo zebrafish model demonstrated that the cardiotoxicity of BDQ was indeed alleviated upon its complexations by the synthetic receptor. Furthermore, our in vitro antibacterial studies suggested that CB[7] formulated BDQ preserved its antimycobacterial efficacy against Mycobacterium smegmatis. Therefore, CB[7] may become a suitable pharmaceutical excipient in formulating BDQ for improving its physiochemical properties (such as solubility), and for alleviating its side effects (such as cardiotoxicity), while the antimycobacterial efficacy of BDQ may be well maintained.

Cucurbit[7]uril: an emerging candidate for pharmaceutical excipients.

Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8, 10, or 13-15), may form host-guest complexes with a variety of small molecules of biomedical interest. The physical and chemical properties of the complexed drugs are often improved as a result of this complexation, suggesting the potential application of CB[7] as a pharmaceutical excipient. This review has summarized the most recent research progress reported between 2011 and early 2017 regarding the biocompatibility of CB[7] and the influence of CB[7] on the stability, solubility, biouptake, and biological activities (including therapeutic efficacies and toxicities) of guest drug molecules. Through this systemic summary and analysis, we intend to stimulate further research efforts in this area and promote the use of CB[7] as an emerging pharmaceutical excipient to improve various properties of drug molecules (or active pharmaceutical ingredients).