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

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Almeida, A (Author) Other; Castro, F (Author) Other; Resende, C (Author) Other; Lucio, M (Author) Other; Schwartz, S (Author) Other; Sarmento, B (Author) Other

Journal

Title: Journal of Controlled Release

Vol. 349

Pages: 731-743

ISSN: 0168-3659

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00W-ZSE

DOI: 10.1016/j.jconrel.2022.07.029

Abstract (EN): 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. In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a sig-nificant 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13