Biopharmaceutical and Nanotoxicological Aspects of Cyclodextrins for Non-Invasive Topical Treatments: A Critical Review.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of its characteristics are low toxicity, biodegradability and biocompatibility. They are divided into α-, β- and γ-cyclodextrins, each with its own particularities. They can undergo surface modification to improve their performance. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading and others. Cyclodextins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles and suppositories) and allow the best topical biological effect of drugs at administration sites such as skin, eyeballs and oral, nasal, vaginal and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other adminsitration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles evaluated to certify that they will be safe and will not cause hearing loss.