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

被引:19
作者
Tramontano, Chiara [1 ,2 ]
Martins, Joao Pedro [3 ]
De Stefano, Luca [1 ]
Kemell, Marianna [4 ]
Correia, Alexandra [3 ]
Terracciano, Monica [2 ]
Borbone, Nicola [2 ]
Rea, Ilaria [1 ]
Santos, Helder A. [3 ,5 ,6 ]
机构
[1] CNR, Inst Appl Sci & Intelligent Syst, Unit Naples, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dept Pharm, I-80131 Naples, Italy
[3] Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Chem & Technol, FI-00014 Helsinki, Finland
[4] Univ Helsinki, Dept Chem, FI-00014 Helsinki, Finland
[5] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, NL-9713 AV Groningen, Netherlands
[6] Univ Groningen, Univ Med Ctr Groningen, WJ Kolff Inst Biomed Engn & Mat Sci, NL-9713 AV Groningen, Netherlands
基金
芬兰科学院;
关键词
colorectal cancer; diatomite nanoparticles; galunisertib; microfluidics; oral drug delivery; CROSS-LINKING STRATEGIES; ADHESION MOLECULE; DELIVERY; GELATIN; EXPRESSION; MIGRATION; TRANSIT; L1CAM; SITE; PH;
D O I
10.1002/adhm.202202672
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 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.
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页数:17
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