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Colorectal cancer has been considered a worldwide public health problem since current treatments are often ineffective. Irinotecan is a frontline chemotherapeutic agent that has dose-limiting side effects that compromise its therapeutic potential. Therefore, it is necessary to develop a novel, targeted drug delivery system with high therapeutic efficacy and an improved safety profile. Here, micellar formulations composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2k) containing irinotecan were proposed as a strategy for colorectal cancer therapy. Firstly, the irinotecan-loaded micelles were prepared using the solvent evaporation method. Then, micelles were characterized in terms of size, polydispersity, zeta potential, entrapment efficiency, and release kinetics. Cytotoxicity and in vivo antitumor activity were evaluated. The micelles showed size around 13 nm, zeta potential near neutral (−0.5 mV), and encapsulation efficiency around 68.5% (irinotecan 3 mg/mL) with a sustained drug release within the first 8 h. The micelles were evaluated in a CT26 tumor animal model showing inhibition of tumor growth (89%) higher than free drug (68.7%). Body weight variation, hemolytic activity, hematological, and biochemical data showed that, at the dose of 7.5 mg/kg, the irinotecan-loaded micelles have low toxicity. In summary, our findings provide evidence that DSPE-mPEG2k micelles could be considered potential carriers for future irinotecan delivery and their possible therapeutic application against colorectal cancer.

Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of cancer, however, it is associated with the occurrence of adverse reactions that limits its clinical use. In this context, the encapsulation of DOX in micelles responsive to pH variations has shown to be a strategy for tumor delivery of the drug, with the potential to increase therapeutic efficacy and to reduce the toxic effects. In addition, radiolabeling nanoparticles with a radioactive isotope is of great use in preclinical studies, since it allows the in vivo monitoring of the nanostructure through the acquisition of quantitative images. Therefore, this study aimed to develop, characterize, and evaluate the antitumor activity of a pH-sensitive micelle composed of DSPE-PEG2000, oleic acid, and DOX. The micelles had a diameter of 13 nm, zeta potential near to neutrality, and high encapsulation percentage. The critical micellar concentration (CMC) was 1.4 × 10−5 mol L-1. The pH-sensitivity was confirmed in vitro through a drug release assay. Cytotoxicity studies confirmed that the encapsulation of DOX into the micelles did not impair the drug cytotoxic activity. Moreover, the incorporation of DSPE-PEG2000-DTPA into the micelles allowed it radiolabeling with the technetium-99 m in high yield and stability, permitting its use to monitor antitumor therapy. In this sense, the pH-sensitive micelles were able to inhibit tumor growth significantly when compared to non-pH-sensitive micelles and the free drug. in vivo toxicity evaluation in the zebrafish model revealed significantly lower toxicity of pH-sensitive micelles compared to the free drug. These results indicate that the developed formulation presents itself as a promising alternative to potentiate the treatment of tumors.