Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics

As cancer being the most difficult disease to treat, different kinds of medications and therapeutic approaches have been prominently developed by scientists. For certain families of drugs, such as immuno-therapeutics or antibody-drug conjugates, efficient delivery systems are required during administration to protect the drugs from chemical degradation or biological inactivation. Delivery systems with the ability to carry different therapeutics or diagnostic agents or both, hold promising potential to tackle the abnormalities behind cancer. In this context, this review provides updated insights on how cyclodextrin-based polymeric nanosystems have become an effective treatment approach against cancer. Cyclodextrins (CDs) are natural oligosaccharides that are famously exploited in pharmaceutical research due to their exceptional quality of entrapping water-insoluble molecules inside their hydrophobic core and providing enhanced solubility with the help of their hydrophilic exterior. Combining the properties of CDs with polymeric nanoparticles (PNPs) brings out excellent versatile and tunable profiles, thanks to the submicron-sized PNPs. By introducing the significance of CD as a delivery system, a collective discussion on different binding approaches and release mechanisms of CD-drug complexation, followed by their characterization studies has been done in this review. Further, in light of recent studies, the article majorly focuses on conveying how promoting CD to a polymeric and nanoscale elevates the multifunctional advantages against cancer that can be successfully applied in combination therapy and theranostics. Moreover, CD-based delivery systems including CALAA-01, CRLX101, and CRLX301, have demonstrated improved tumor targeting, reduced side effects, and prolonged drug release in preclinical studies and clinical trials.