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 Świderska-Środa , Agnieszka Chodara , Jacek Wojnarowicz , Urszula Szałaj , Samar A. Shahein , Ahmed M. Aboul-Enein , Faten Abou-Elella , Stanisław Gierlotka , Tomasz Ciach , Witold Łojkowski

Abstract

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.
Author Khaled AbouAitah
Khaled AbouAitah,,
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, Agata Stefanek (FCPE / DBBE)
Agata Stefanek,,
- Department of Biotechnology and Bioprocess Engineering
, Iman M. Higazy
Iman M. Higazy,,
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, Magdalena Janczewska (FCPE / DBBE)
Magdalena Janczewska,,
- Department of Biotechnology and Bioprocess Engineering
, Anna Świderska-Środa - Instytut Wysokich Ciśnień Polskiej Akademii Nauk (Instytut Wysokich Ciśnień Polskiej Akademii Nauk)
Anna Świderska-Środa,,
-
, Agnieszka Chodara - Instytut Wysokich Ciśnień Polskiej Akademii Nauk (Instytut Wysokich Ciśnień Polskiej Akademii Nauk)
Agnieszka Chodara,,
-
, Jacek Wojnarowicz - Instytut Wysokich Ciśnień Polskiej Akademii Nauk (Instytut Wysokich Ciśnień Polskiej Akademii Nauk)
Jacek Wojnarowicz,,
-
, Urszula Szałaj
Urszula Szałaj,,
-
, Samar A. Shahein
Samar A. Shahein,,
-
, Ahmed M. Aboul-Enein
Ahmed M. Aboul-Enein,,
-
et al.`
Journal seriesPharmaceutics, ISSN 1999-4923
Issue year2020
Vol12
No1
Pages1-28
Article number70
Keywords in Englishhydroxyapatite 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
ASJC Classification3003 Pharmaceutical Science
DOIDOI:10.3390/pharmaceutics12010070
URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022489/
Languageen angielski
File
AbouAitah, K. (i in.) - Effective targeting of...pdf 9.72 MB
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 18-08-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus Citations = 0; GS Citations = 3.0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.097; WoS Impact Factor: 2018 = 4.773 (2)
Citation count*3 (2020-08-27)
Additional fields
FundingWe would like to thank the National Research Centre (NRC, Egypt) for supporting this work. We also wish to thank the National Center for Research and Development, Poland (STRATEGMED3/306888/3/ NCBR/2017, project iTE, Poland). This research was carried out using equipment funded by the CePT project (reference no. POIG.02.02.00-14-024/08), financed by the European Regional Development Fund within the Operational Programme “Innovative Economy” for 2007–2013.
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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