Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

Abstract

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the β-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/β-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/β-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

Rutin-Functionalized Multi-Walled Carbon Nanotubes: Molecular Docking, Physicochemistry and Cytotoxicity in Fibroblasts

“…The bidding affinities of CNT_RUT_HP_AA were calculated using the AutoDock Vina 1.1.2 [ 17 , 18 ]. CNT_RUT_HP_AA structure (molecular formula: C 176 H 222 O 60 ) was created using Discovery Studio, v20 (Accelrys, San Diego, CA, USA), and applied to Chem3D-MM2 protocol for energy minimization.…”

Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study

“…The prediction was validated in an in vitro assay where the cellular uptake of these nanoparticles was eight-fold higher in comparison to conventional systems in FR-positive tumour cells via endocytosis. In another study, docking was used to predict the conformation of a POH/β-CD inclusion complex of which the predicted most stable structure (1:1 molar ratio) was selected for formulation and in vitro and in vivo studies [25].…”

Synthesis and Characterization of an Inclusion Complex of dl-Aminoglutethimide with β-Cyclodextrin and Its Innovative Application in a Biological System: Computational and Experimental Investigations

“…Molecular docking gives us effective information about bond simulations between molecules. 27 In order to comprehend the orientation, conformation, and interaction of the drug/guest molecule within the cavity of β-CD, molecular modeling is a constructive computational technique. 28 …”