Abstract:
Colorectal cancer (CRC) is the fourth most common cancer worldwide and the third leading cause of death in 2022 as depicted by the World Health Organization. It is estimated that by 2040, 2.9 million people will be affected by this pathology. Although several synthetic chemotherapeutic agents have been used to treat CRC, they do not specifically target malignant cells, which leads to severe side effects and substantial damage to healthy cells. While targeted therapies have emerged as more efficacious alternatives due to their selective action against cancer cells, their prohibitive cost remains a major limitation. Consequently, many alternative safer and cheaper therapies have been extensively studied against CRC mainly based on repurposing and nanoformulating drugs. Metformin, for example, is one of the most prescribed oral glucose-lowering drug (GLD) for type-2- diabetes mellitus and has been investigated owing to its therapeutic and pharmacological potential. Due to its multitargeting capabilities, metformin interferes with many tumorigenic pathways and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis. Despite its promising therapeutic activity, metformin has not yet reached clinical trials as an anti-cancer drug, restricted by its short half-life, limited absorption, and low bioavailability. In an effort to address these issues, nanoparticulate systems, like polymeric nanocarriers, have improved metformin's bioavailability, controlled release, and capacity to bypass various biological barriers. Thus, the current study aims to design a polymeric double emulsion to ameliorate metformin anticancer effects. The double emulsion was prepared using the solvent evaporation technique and characterized according to its particle size, polydispersity index (PDI), and surface charge. The results showed a nanometric size of metformin-loaded nanoparticles 130.93 ± 8.91 nm, unimodal particle size distribution 0.10 ± 0.03, and a positive charge of value +1.19 ± 0.58 mV. Moreover, metformin was successfully encapsulated within polymeric nanoparticles as it demonstrated an in-vitro significantly enhanced dissolution behavior. Furthermore, the cytotoxic behavior provided evidence that the anticancer effect of the loaded NPs on HT29 cells showed favorable effects at highest concentration being 5 mM after 72 hr in comparison to free metformin. Therefore, PNPs proved to be prospective nanocarriers that could be used for the delivery of repurposed drugs like metformin in CRC therapy.
