Oral delivery of camptothecin-loaded multifunctional chitosan-based micelles is effective in reduce colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease with high incidence and mortality worldwide. The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles. In this work, camptothecin (CPT), a potent anticancer drug, was loaded into an amphiphilic chitosan modified with PEG and oleic acid, to reduce CRC progression after oral administration. While CPT-loaded micelles presented anticancer activity against HCT116, Caco-2 and HT29 CRC cell lines in vitro, empty micelles demonstrated a safe profile when incubated with human blood cells and colorectal cancer cell lines.

Highlights

• CPT-loaded micelles demonstrated in vitro anticancer activity against CRC cancer cell lines and 3D intestinal spheroids.
• In an in vivo xenograft model, chitosan micelles were able to delay tumor growth.
• In a CRC animal model, drug-loaded micelles decreased tumor development and progression after oral administration.

In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a significant effect on the spheroid’s metabolic activity and size reduction. Remarkably, in vivo studies performed in a HCT116 xenograft model, showed a significant reduction on the tumor growth during and after treatment with CPT-loaded micelles. Moreover, in a more biological relevant in vivo model of chemically-induced CRC, orally administered CPT-loaded micelles demonstrated a significant reduction on tumor incidence and inflammation signs. The findings here reported indicate that CPT-loaded into chitosan-based micelles, by improving drug solubility, alongside its safety profile for normal tissues, may have a promising role CRC chemotherapy.

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Andreia Almeida, Flávia Castro, Carlos Resende, Marlene Lúcio, Simó Schwartz, Bruno Sarmento,
Oral delivery of camptothecin-loaded multifunctional chitosan-based micelles is effective in reduce colorectal cancer, Journal of Controlled Release, Volume 349, 2022, Pages 731-743, ISSN 0168-3659,
https://doi.org/10.1016/j.jconrel.2022.07.029.