| Přispěvatelé: |
Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Nanomedicines and Biomedical Engineering, Department of Chemistry, Helsinki One Health (HOH), Drug Research Program, Divisions of Faculty of Pharmacy, Tramontano, Chiara, Pedro Martins, Joāo, De Stefano, Luca, Semel, Marianna, Correia, Alexandra, Terracciano, Monica, Borbone, Nicola, Rea, Ilaria, Almeida Santos, Hélder |
| Popis: |
The oral route is highly desirable for colorectal cancer (CRC) treatment because it allows concentrating the drug in the colon and achieving a localized effect. However, orally administered drugs are often metabolized in the liver, resulting in reduced efficacy and the need for higher doses. Nanoparticle-based drug delivery systems can be engineered to prevent the release of the drug in the stomach, addressing the release at the target site and enhancing the efficacy of the delivered drug. Here, we develop an orally administrable galunisertib delivery system made of gelatin-covered diatomite nanoparticles modified with an antibody targeting the L1-CAM on metastatic cells, and further encapsulated in an enteric matrix by microfluidics. The gastro-resistant polymer protects the nanoparticles from the action of the digestive enzymes and allows for a sustained release of galunisertib at the intestinal pH. The efficacy of antibody-antigen interactions to drive the internalization of nanoparticles in the targeted cells is investigated in CRC cells expressing abnormal (SW620) or basal levels (Caco-2, HT29-MTX) of L1-CAM. The combination of local drug release and active targeting enhances the effect of the delivered galunisertib, which inhibits the migration of the SW620 cells with greater efficiency compared to the free drug. This article is protected by copyright. All rights reserved. |
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