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Partial inclusion complex assisted crosslinked ß-cyclodextrin nanoparticles for improving therapeutic potential of docetaxel against breast cancer.
Jain S, Desai MR, Nallamothu B, Kuche K, Chaudhari D, Katiyar SS. Partial inclusion complex assisted crosslinked ß-cyclodextrin nanoparticles for improving therapeutic potential of docetaxel against breast cancer. Drug delivery and translational research. 2021 Mar 27.
The present investigation demonstrates the development of crosslinked ß-cyclodextrin nanoparticles (ß-CD NPs) for enhancing the therapeutic efficacy of docetaxel (DTX) against breast cancer. Initially, a partial inclusion complex between ß-CD and polypropylene glycol (PPG) was formed to induce self-assembly. This was followed by crosslinking of ß-CDs using epichlorohydrin (EPI) and removal (by solubilization) of PPG to yield uniform ß-CD NPs. The formed particles were used for loading DTX to form DTX ß-CD NPs. The resultant DTX ß-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 ß-CD NPs in comparison to free DTX. Moreover, pharmacokinetic evaluation of DTX ß-CD NPs revealed ~2 and ~5-fold increase in AUC and mean residence time (MRT) of DTX when compared to Docepar. Further, the anti-tumor activity using DMBA-induced cancer model showed that DTX ß-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 ß-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 ß-CD NPs which can be effectively utilized for improving the therapeutic efficacy of DTX.