• characterization
• colorectal cancer
• formulation
• Irinotecan
• nanoparticles
• nanoprecipitation
• oral administration
• resazurin
• Zein

Colorectal cancer (CRC) is one of the world’s most common and deadly cancers, mainly due to its metastatic and metabolic ability. The common chemotherapeutic treatment for metastatic CRC consists of regimens with a combination of 5-fluorouracil (5-FU) with leucovorin and oxaliplatin (FOLFOX) and 5-FU with leucovorin and irinotecan (FOLFIRI), for intravenous administration. These kinds of approaches are associated with significant side effects, resistance to the treatment and difficult administration. Recent studies in literature showed about the use of Zein nanoparticles (NPs) to improve bioavailability and reduce the side effect of this combination drugs. Zein protein may constitute an inexpensive, safe, and effective choice as a matrix to produce NPs loaded with hydrophobic molecules , as Irinotecan Hydrochloride Trihydrate (IRTH) for oral administration.

In this work, it was loaded IRTH into Zein NPs by using a nanoprecipitation method. The formulations were characterized by dynamic light scattering (DLS) resulting in the size range of 210- 230 ± 6 nm, PdI 0.223 ± 0.020 and Zeta potential +23 ± 1 mV. The association efficiency and drug loading of IRTH were analyzed by indirect method (AE=70±5 % DL=3.4±0.24 %) and direct method. Finally, after a suitable evaluation, it was followed the cytotoxicity assay was followed in two different cells line, HT29-MTX and HCT116, both human colonic epithelial metastatic lines. After, the permeability studies of IRTH in a co-culture of Caco-2 and HT29-MTX were performed.
The results showed a potential formulation but more investigation is needed to confirm a great stability of that over time and suitable intestinal permeability after the oral administration. Moreover, in vivo assay can be useful to know about the bioavailability and side effects.