Folate receptor targeted bufalin/β-cyclodextrin supramolecular inclusion complex for enhanced solubility and anti-tumor efficiency of bufalin

•It is the first time to synthesis BF/β-CD inclusion complex and FA targeted inclusion complex.•The BF/β-CD inclusion complex with IE of (94.22 ± 0.85) % and DL of (14.11 ± 0.20) % were much higher than other bufalin. carriers.•FA targeted inclusion complex significantly enhanced the solubility, cell uptake and antitumor efficiency of bufalin.

Bufalin (BF), a traditional Chinese medicine, exhibited inhibitory activities against a broad spectrum of tumor cells. The present study elaborates that bufalin was successfully encapsulated into the cavity of β-cyclodextrin (β-CD), which was determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The best reaction mole ratio of BF/β-CD was 1:5. The solubilities of bufalin in water and phosphate buffer solution (pH = 7.4) were increased up to 24 and 34 times after encapsulated into the cavity of β-CD respectively. The inclusion efficiency (IE) and drug loading (DL) of bufalin in the inclusion complex were (94.22 ± 0.85)% and (14.11 ± 0.20)%, respectively. Then β-CD conjugated with folic acid (FA) were further prepared and employed to improve the anti-tumor efficacy of inclusion complex. The in vitro dissolution and solubility study showed better values of inclusion complex and FA targeted inclusion complex than that of pure BF. Cytotoxicity experiments by using HCT116 cell line revealed that the antitumor efficiency of bufalin were enhanced more than two folds in the presence of β-CD and folate conjugated β-CD (FA-PEI-β-CD), which demonstrated the potential application of β-CD (FA-PEI-β-CD) as delivery vehicles of bufalin for antitumor therapy.

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