β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

International Journal of Molecular Sciences

Rosa Iacovino¹  Filomena Rapuano²  Jolanda Valentina Caso¹  Agostino Russo¹  Margherita Lavorgna¹  Chiara Russo¹  Marina Isidori¹  Luigi Russo¹  Gaetano Malgieri¹ 

[1] Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100 Caserta, Italy; E-Mails:;Department of Biological and Environmental Science, University of Sannio, Via Port’Arsa 11, 82100 Benevento, Italy; E-Mail:

关键词: β-cyclodextrin;    pipemidic acid;    inclusion complex;    microbial activity;    antitumoral activity;   

DOI  :  10.3390/ijms140713022

来源: mdpi

【 摘 要 】

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland