Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles
| Autor: | Witold Lojkowski, Khaled AbouAitah, Stanislaw Gierlotka, Faten Abou-Elella, Urszula Szałaj, Agata Stefanek, Magdalena Janczewska, Tomasz Ciach, Ahmed M. Aboul-Enein, Samar A Shahein, Agnieszka Chodara, Jacek Wojnarowicz, Anna Swiderska-Sroda, Iman M Higazy |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
in vitro release kinetics
natural products nanoformulations lcsh:RS1-441 Pharmaceutical Science 02 engineering and technology delivery system for cancer targeting 010402 general chemistry 01 natural sciences Article lcsh:Pharmacy and materia medica chemistry.chemical_compound folic acid stomatognathic system medicine Cytotoxicity Alkaloid Cancer colon cancer cells and spheroids pH-sustained release effect Prodrug 021001 nanoscience & nanotechnology medicine.disease Combinatorial chemistry In vitro 0104 chemical sciences Targeted drug delivery chemistry piperine alkaloid prodrug Piperine Surface modification lipids (amino acids peptides and proteins) 0210 nano-technology hydroxyapatite nanocarrier |
| Zdroj: | Pharmaceutics Volume 12 Issue 1 Pharmaceutics, Vol 12, Iss 1, p 70 (2020) |
| 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: | OpenAIRE |
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