Microfluidic‐Assisted Production of Gastro‐Resistant Active‐Targeted Diatomite Nanoparticles for the Local Release of Galunisertib in Metastatic Colorectal Cancer Cells

• DOI: 10.1002/adhm.202202672
• Publication Date: 2022-12-02T17:41:50Z
• Authors: Chiara Tramontano; João Pedro Martins; Luca De Stefano; Marianna Kemell; Alexandra Correia; Monica Terracciano; Nicola Borbone; Ilaria Rea; Hélder A. Santos
• Keywords: oral drug delivery; Microfluidics; Galunisertib; microfluidics; colorectal cancer; Pharmacy; 03 medical and health sciences; Drug Delivery Systems; Humans; Research Articles; 0303 health sciences; Stomach; diatomite nanoparticles; diatomite nanoparticles colorectal cancer; Colorectal cancer; 3. Good health; Chemical sciences; galunisertib; Pharmaceutical Preparations; microfluidics, oral drug delivery, galunisertib, diatomite nanoparticles colorectal cancer; Colonic Neoplasms; Diatomite nanoparticles; Nanoparticles; Oral drug delivery; Caco-2 Cells

AbstractThe 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 diffusion of the drug in the stomach, addressing the release at the target site, and enhancing the efficacy of the delivered drug. Here, an orally administrable galunisertib delivery system is developed with gelatin‐covered diatomite nanoparticles targeting the ligand 1‐cell adhesion molecule (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.