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

Abstract

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).

Applications of Cucurbit[n]urils (n=7 or 8) in Pharmaceutical Sciences and Complexation of Biomolecules

“…As the complexations of drug molecules by CB [7] or CB [8] often improve the stability, solubility and pKa values of the guest drugs, [5] it has been generally expected that the biological activities, particularly therapeutic efficacies, of guest drug molecules are modulated upon complexations. Thus we are summarizing these recent efforts basd on the indications/ actions of these guest drug molecules in this section.…”

“…[33] Their in vitro test showed that the supramolecular encapsulation by CB [8] enhanced the inhibitory effect of carboxin on R. solani. [33] Later, Saleh and co-authors investigated the interactions of fuberidazole (FBZ) fungicide with CB [5], CB [7] and CB [8], respectively. [34] Due to the small cavity, FBZ cannot form a stable complex with CB [5].…”

“…[33] Later, Saleh and co-authors investigated the interactions of fuberidazole (FBZ) fungicide with CB [5], CB [7] and CB [8], respectively. [34] Due to the small cavity, FBZ cannot form a stable complex with CB [5]. However, FBZ formed a stable complex with CB [7] with a moderate binding constant K a of 5.0 3 10 2 M À1 in the neutral form and 3.2 3 10 5 M À1 in the protonated form, along with a pK a shift of 3.8 units.…”

“…[3] CB[n]s with different sizes (as is tuned by n) exhibit various properties. [4][5] For instance, our group, has demonstrated the influence of encapsulation by CB [7] on the physical and chemical properties of small organic molecules of biological interest [6] and gradually proceeded to employ these macrocycles to develop supramolecular pharmaceutics. [4] These properties have attracted much attention from scientists.…”

“…CB [7] (Figure 1) has outstanding water solubility among the CB[n] family and ultrahigh binding affinities with some specific compounds that rival some of the highest binding affinities found in Nature. [5] Upon encapsulation by CB [7], a variety of drug molecules have exhibited enhanced bioavailability, [7] improved water solubility, [8] modulated efficacy [9] and reduced toxicity. [4][5] For instance, our group, has demonstrated the influence of encapsulation by CB [7] on the physical and chemical properties of small organic molecules of biological interest [6] and gradually proceeded to employ these macrocycles to develop supramolecular pharmaceutics.…”