Partial inclusion complex assisted crosslinked β-cyclodextrin nanoparticles for improving therapeutic potential of...

The present investigation demonstrates the development of crosslinked β-cyclodextrin nanoparticles (β-CD NPs) for enhancing the therapeutic efficacy of docetaxel (DTX) against breast cancer. Initially, a partial inclusion complex between β-CD and polypropylene glycol (PPG) was formed to induce self-assembly. This was followed by crosslinking of β-CDs using epichlorohydrin (EPI) and removal (by solubilization) of PPG to yield uniform β-CD NPs. The formed particles were used for loading DTX to form DTX β-CD NPs. The resultant DTX β-CD NPs exhibited particle size of 223.36 ± 17.73 nm with polydispersity index (PDI) of 0.13 ± 0.09 and showed entrapment efficiency of 54.53 ± 2%. Increased cell uptake (~5-fold), cytotoxicity (~3.3-fold), and apoptosis were observed in MDA-MB-231 cells when treated with DTX β-CD NPs in comparison to free DTX. Moreover, pharmacokinetic evaluation of DTX β-CD NPs revealed ~2 and ~5-fold increase in AUC_0-∞ and mean residence time (MRT) of DTX when compared to Docepar^®. Further, the anti-tumor activity using DMBA-induced cancer model showed that DTX β-CD NPs were capable of reducing the tumor volume to ~40%, whereas Docepar^® was able to reduce tumor volume till ~80%. Finally, the toxicity evaluation of DTX β-CD NPs revealed no short-term nephrotoxicity and was confirmed by estimating the levels of biomarkers and histopathology of the organs. Thus, the proposed formulation strategy can yield uniformly formed β-CD NPs which can be effectively utilized for improving the therapeutic efficacy of DTX.