Multifunctional application of supramolecular cucurbiturils as encapsulating hosts in drug delivery: A review

Cucurbit[n]uril (CB[n], n = 5–10), a unique category of molecular hosts composed of n glycoluril units, has attracted considerable attention because of its exceptional molecular recognition properties. Cucurbit[n]urils represent an innovative category of molecular containers capable of forming stable complexes with a wide array of guests, including pharmaceutical compounds, amino acids, proteins or peptides, saccharides, and dyes, among others. Compared to the chemistry of calixarenes and cyclodextrins, the advancement of CB[n] chemistry has been rather sluggish until recently. This is mainly due to their inadequate solubility in typical solvents and the difficulties involved in functionalising these compounds. Cucurbiturils are characterised as water-soluble, symmetrical, rigid host molecules with a pumpkin-like form. The distinctiveness of cucurbiturils facilitates the encapsulation of diverse pharmacological molecules, both neutral and positively charged, via non-covalent interactions, yielding femtomolar affinities. This feature article summarises numerous studies conducted by researchers on the applicability of cucurbiturils and their derivatives in targeted medication delivery and controlled drug release. In vitro and in vivo experiments indicate that cucurbit[n]urils possess negligible systemic toxicity, exhibit specific organ toxicity, and do not seem to affect embryonic biology. Drug delivery methods that improve upon those of other supramolecular host molecules, especially cyclodextrins, and alternative formulation systems like polymers, hydrogels, and liposomes are anticipated to be developed as a result of the increasing fascination with cucurbituril-based systems, which are known for their low acute toxicity. The case studies show a wide range of usage, from basic research to translational uses in fields including gene therapies, antibiotics, and chemotherapy, among others.