Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles
Khaled AbouAitah,
Agata Stefanek,
Iman M. Higazy,
Magdalena Janczewska,
Anna Swiderska-Sroda,
Agnieszka Chodara,
Jacek Wojnarowicz,
Urszula Szałaj,
Samar A. Shahein,
Ahmed M. Aboul-Enein,
Faten Abou-Elella,
Stanislaw Gierlotka,
Tomasz Ciach,
Witold Lojkowski
Affiliations
Khaled AbouAitah
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
Agata Stefanek
Biomedical Engineering Laboratory, Faculty of Chemical and Process Engineering, Warsaw University of Technology, 00-645 Warsaw, Poland
Iman M. Higazy
Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), P.C. 12622 Dokki Giza, Egypt
Magdalena Janczewska
Biomedical Engineering Laboratory, Faculty of Chemical and Process Engineering, Warsaw University of Technology, 00-645 Warsaw, Poland
Anna Swiderska-Sroda
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
Agnieszka Chodara
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
Jacek Wojnarowicz
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
Urszula Szałaj
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.
