Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer

The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular upta...

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Published inPharmaceutics Vol. 14; no. 4; p. 768
Main Authors Shih, Ying-Hsia, Peng, Cheng-Liang, Chiang, Ping-Fang, Shieh, Ming-Jium
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 31.03.2022
MDPI
Subjects
Biodistribution
Cancer therapies
Colorectal cancer
Copolymers
Cytotoxicity
Drug delivery systems
Drug dosages
Efficiency
FDA approval
Kinases
Laboratory animals
Molecular weight
NMR
Nuclear magnetic resonance
polymeric micelles
Polymers
SN-38
sunitinib
Tumors
Vascular endothelial growth factor
United Kingdom > UK
United States > US
Taiwan
sunitinib
SN-38
colorectal cancer
polymeric micelles
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Summary:The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake in HCT-116 cells. Then, subcutaneous HCT-116 xenograft tumors were used for ex vivo biodistribution, antitumor efficacy, and histochemical analysis studies. Results of cellular uptake and ex vivo biodistribution of SN-38/Sunitinib micelles showed the highest accumulation in tumors compared with other normal organs. In the antitumor effect studies, mice bearing HCT-116 tumors were smallest at day 28 after injection of SN-38/Sunitinib micelles, compared with other experiment groups (p < 0.01). As demonstrated by the results of inhibition on multi-receptors by Sunitinib, we confirmed that SN-38/Sunitinib co-loaded micelles to be a treatment modality that could inhibit VEGF and PDGF receptors and enhance the antitumor effect of SN-38 (p < 0.05). In summary, we consider that this micelle is a potential formulation for the combination of SN-38 and Sunitinib in the treatment of colorectal cancer.
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ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14040768