Encapsulation of Drug Molecules by Cucurbiturils: Effects on their Chemical Properties in Aqueous Solution

Abstract

The effects of the encapsulation of drugs and other molecules of biomedical interest by cucurbit[n]uril (n = 5-8, 10) host molecules on the chemical properties of the drugs in aqueous solution are reviewed. The cucurbituril complexation of drug molecules has been shown to generally increase the guests' pK a values through preferential inclu-sion of the protonated species, modulate other equilibria involving the guest, improve the solubility in aqueous solution, reduce the toxicity and other side effects, as well as enhance the stability and targeted delivery of the drug molecule. These benefits have led to an increasing interest in the applications of cucurbit[n]urils in novel drug formulations.

A photoinduced pH jump applied to drug release from cucurbit[7]uril

“…26,27 As a consequence of the increased affinity of CBs for cationic species, 28 they display a pronounced preference for binding the protonated forms of guests over their neutral forms. 8,29,30 Accordingly, host-guest binding of CBs is strongly pH-dependent and the differential binding manifests itself in complexationinduced pK a shifts. 18,30,31 Invariably, when basic guests are investigated, their affinity increases at low pH and decreases at high pH.…”

Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study

“…CB[n]s consist of n glycoluril units that are connected by n pairs of methylene groups, with a lipophilic cavity in the middle that is accessible by a variety of guest molecules via two polar carbonyl-laced portals [3,4]. Due to its superior water-solubility, CB [7] (Figure 1) is a particularly attractive capsule to host a variety of guest molecules of biomedical and medical interest, both in vitro and in vivo [1,2].…”

Sequential inclusion of two berberine cations in cucurbit[8]uril cavity: kinetic and thermodynamic studies

“…[45][46] CBn hosts have considerable potential in the delivery, stabilization, solubilization and controlled release of drugs. [47][48] We have demonstrated that berberine (B + ), a pharmaceutically important isoquinoline alkaloid, is an excellent guest for the investigation of the complex formation dynamics with CB7. 44 Activation enthalpy of 32 and 69 kJ mol −1 were found for the association and dissociation implying that the tight carbonyl-laced portal of the host constituted a steric barrier.…”