Cyclodextrins (CyDs) in nano drug delivery systems have received much attention in pursuit of good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. Their unique internal cavity has widened the application of CyDs in drug delivery based on its advantages. Besides this, the polyhydroxy structure has further extended the functions of CyDs by inter- and intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to alteration of the physicochemical characteristics of the drugs, significant therapeutic promise, a stimulus-responsive switch, a self-assembly capability, and fiber formation. This review attempts to list recent interesting strategies regarding CyDs and discusses their roles in nanoplatforms, and may act as a guideline for developing novel nanoplatforms. Future perspectives on the construction of CyD-based nanoplatforms are also discussed at the end of this review, which may provide possible direction for the construction of more rational and cost-effective delivery vehicles.

Purpose: This study aims to design and characterize Oligomeric Proanthocyanidin-Tetrandrine nanoparticles (OPC-Tet NPs) in alleviating progress of osteoarthritis (OA) by anti-inflammatory and anti-ferroptosis mechanism. Methods: A carrier-free drug delivery system (DDS) has been designed based on OPC and Tet with the unification of medicines and excipients. In vitro studies have evaluated biosafety, cellular internalization, suppression of oxidative stress, and maintaining iron homeostasis in RAW 264.7 cells. The treatment efficacy and mechanism were investigated by using the papain-induced OA mouse model. Results: OPC and Tet were successfully self-assembled into NPs with a particle size of 153 nm approximately, exhibiting a spherical morphology, and narrow size distribution. In vitro results indicated that OPC-Tet NPs exhibit good biocompatibility with 78.4% cell viability at a concentration of 40 μg/mL. The results from micro-CT and pathological staining demonstrate that OPC-Tet NPs can effectively improve bone volume fraction (BV/TV [%]) by 30.5% compared to model group (P < 0.001). Furthermore, IHC experiments showed that OPC-Tet NPs could mediate inflammation and ferroptosis to manage OA. Conclusion: In summary, our results demonstrate OPC-Tet NPs show good biocompatibility, and treatment effect. The treatment mechanism of anti-inflammation and anti-ferroptosis were also verified. The current research not only offers a new strategy to manage OA but also provides more possibilities for potential application of natural products.