Ferulic acid nanocapsules as a promising treatment modality for colorectal cancer: Preparation and in vitro/in vivo appraisal

Ferulic acid is a polyphenolic compound with proven anticancer properties, but it suffers from low solubility and bioavailability. In the current work, polymeric and lipidic nanocapsules of ferulic acid were prepared, characterized, and tested on colorectal cancer (CRC) cell lines (HCT-116 and Caco2 cells), with mechanistic anticancer elucidation using flow cytometry. The selected NCs formulation was further tested in vivo on rats after inducing CRC using 1,2 dimethylhydrazine (DMH), followed by biochemical analysis, molecular and histological examinations.Results revealed that both polymeric and lipidic nanocapsules showed favorable properties, but the latter was smaller in size and presented higher cumulative percent released of FA. The lipidic nanocapsules displayed better anticancer activity than the drug on both cell lines; with apoptosis being the dominant cell death mode. The in vivo study revealed that ferulic acid lipid NCs exhibited significant antioxidant and anti-inflammatory activities. They also downregulated cyclin D1, IGF II, and VEGF, and autoregulated the apoptotic/anti-apoptotic gene BAX/Bcl-2; indicating their apoptotic and anti-angiogenic potential, which was further confirmed by histological examination.Findings prove that the proposed ferulic acid lipid nanocapsules are an ideal system for treatment of CRC, and can serve as a preventive measure against metastasis.