Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model
Allan A. Rezende,
Rafael S. Santos,
Luciana N. Andrade,
Ricardo G. Amaral,
Matheus M. Pereira,
Cristiane Bani,
Mo Chen,
Ronny Priefer,
Classius F. da Silva,
Ricardo L. C. de Albuquerque Júnior,
Eliana B. Souto,
Patrícia Severino
Affiliations
Allan A. Rezende
University of Tiradentes (Unit), Postgraduate Program Industrial Biotechnology, and Health and Enviroment. Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil
Rafael S. Santos
University of Tiradentes (Unit), Postgraduate Program Industrial Biotechnology, and Health and Enviroment. Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil
Luciana N. Andrade
Department of Physiology, Federal University of Sergipe, São Cristovão, 49100-000 Sergipe, Brazil
Ricardo G. Amaral
Department of Physiology, Federal University of Sergipe, São Cristovão, 49100-000 Sergipe, Brazil
Matheus M. Pereira
CICECO, Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Cristiane Bani
Department of Physiology, Federal University of Sergipe, São Cristovão, 49100-000 Sergipe, Brazil
Mo Chen
Department of Gynecology, Obstetrics & Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Ronny Priefer
School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USA
Classius F. da Silva
Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, 09972-270 Diadema, São Paulo, Brazil
Ricardo L. C. de Albuquerque Júnior
University of Tiradentes (Unit), Postgraduate Program Industrial Biotechnology, and Health and Enviroment. Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil
Eliana B. Souto
Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
Patrícia Severino
University of Tiradentes (Unit), Postgraduate Program Industrial Biotechnology, and Health and Enviroment. Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil
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.
