Ferulic acid nanocapsules as a promising treatment modality for colorectal cancer: Preparation and in vitro/in vivo appraisal
Graphical abstract
Introduction
Colorectal cancer is one of the most commonly diagnosed cancers, and is the second leading cause of cancer death worldwide [1]. Familial history, age, sex, genetic and environmental factors are associated with colon and rectal cancer. Surgical intervention is the first treatment option, although micrometastatic lesions may occur at the site of surgical operation [2]. Adjuvant chemotherapy is also used in the treatment of colon cancer in the advanced stages (Stage III and above) that include lymph node involvement or metastasis; however, this modality is associated with severe reported side effects.
Till current date, several studies have proven that the use of nanoparticles in cancer treatment could overcome several challenges within the tumor microenvironment such as immune suppression, vascular permeability, and tissue hypoxia, through passive targeting and enhanced permeability and retention (EPR effect) [3], [4], [5], and using specific targeting ligands [3], [6], [7]. Moreover, there is a great interest in the investigation of the potential role of herbal and complementary medicines in the treatment of different cancer subtypes, due to their immunoregulatory, tumor inhibitory properties, and antioxidant activities [8], [9]. Ferulic acid (FA) is a polyphenolic compound (4-hydroxy-3-methoxycinnamic acid), which exerts diverse therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties on several types of cancers [10], [11], [12]. FA is also able to decrease the occurrence of azoxymethane-induced large bowel neoplasms, hence manifesting chemopreventive potential on colonic neoplasia [13]. Despite of the pharmacological merits of FA, its low solubility and bioavailability in aqueous medium hinder its widespread application and clinical implementation. One of the proposed approaches to overcome the aforementioned problems is the formulation of FA in nanoparticulate carriers, such as nanoemulsions, chitosan nanoparticles and solid lipid nanoparticles [12], [14], [15].
Among the different types of nanoparticles, polymeric and lipidic nanocapsules hold great interest. Polymeric nanocapsules (PNCs) comprise a polymer coat surrounding an oil core [3]. Similarly, LNCs consist of an oily core surrounded by the amphiphilic surfactant solutol acting as a shell. LNCs are considered as stealth microemulsions with the added advantages of being small-sized nanocarriers, which makes them an excellent candidate for tumor targeting and uptake. Furthermore, LNCs hold further advantage over PNCs where the use of organic solvents is omitted; resulting in safer delivery systems for human use. To the best of our knowledge, no other studies reported the formulation of LNCs for FA till current date.
Therefore, following this context, the present work focused on preparing, characterizing and comparing PNCs and LNCs of FA, and studying the possible effects of the selected nanoencapsulated FA formulation against colon cancer both in vitro and in vivo.
Section snippets
Materials
Ferulic acid was purchased from Skinactives Company, USA. Labrafac Lipophile WL 1349 oil was kindly gifted by Gattefossé Company, France. Soybean phosphatidylcholine (Epikuron E145V & Epikuron 200) were kindly gifted by Cargill Company, Germany. Polylactide-glycolide (PLGA) grade 7502 A was kindly gifted by Purac Company, Netherlands. Poloxamer P407 was kindly gifted by BASF Company, Germany. Potassium dihydrogen phosphate, tween 80, orthophosphoric acid, disodium hydrogen phosphate, as well as
Preparation and characterization of FA loaded PNCs and LNCs
Two types of NCs formulations of FA were prepared, characterized and compared in this study with the aim of identifying the best NCs formulation for enhancing the anticancer activity of FA against colon cancer cells. For the PNCs, they were prepared using the nanoprecipitation method [16], [17]. The previously reported biodegradability [29], [30] and biocompatibility of PLGA polymer delineated it as a promising platform for the preparation of PNCs for delivery of anticancer molecules [3], [21],
Conclusions
Two types of ferulic acid loaded nanocapsules; polymeric and lipidic were prepared and characterized in the current study. Lipidic nanocapsules were proven superior to polymeric nanocapsules on the cellular level, and their promising therapeutic potential were further delineated in an in vivo model of colorectal cancer. Results of the current study draw the attention to the importance of nutraceuticals such as ferulic acid in treatment of cancer, as well as the promising nature of lipidic
CRediT authorship contribution statement
Riham I. El-Gogary: Conceptualization, Data curation, Investigation, Formal analysis, Writing – original draft. Maha Nasr: Conceptualization, Data curation, Methodology, Validation, Writing – review & editing. Laila A. Rahsed: Conceptualization, Data curation, Investigation, Formal analysis, Writing – original draft. Mohamed A. Hamzawy: Conceptualization, Data curation, Investigation, Formal analysis, Writing – original draft.
Declaration of competing interest
This work was implemented with the support of the Arab-German Young Academy of Sciences and Humanities (AGYA), which draws on financial support from the German Federal Ministry of Education and Research (BMBF) grant 01DL20003.
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