Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles

Autor:	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
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	hydroxyapatite nanocarrier piperine alkaloid prodrug natural products delivery system for cancer targeting nanoformulations colon cancer cells and spheroids in vitro release kinetics ph-sustained release effect folic acid Pharmacy and materia medica RS1-441
Zdroj:	Pharmaceutics, Vol 12, Iss 1, p 70 (2020)
Druh dokumentu:	article
ISSN:	1999-4923
DOI:	10.3390/pharmaceutics12010070
Popis:	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.
Databáze:	Directory of Open Access Journals
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