Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 51, Issue -, Pages 721-735Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2019.03.003
Keywords
Biodegradable polymer; Surface modification; Combination therapy; Colon cancer; Hydroxytyrosol
Categories
Funding
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran [71/95]
- student of medical biotechnology
- student of medical nanotechnology at Tabriz University of medical sciences
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A potential approach for clinical colon cancer therapy is combination chemotherapy. In this study, a biodegradable and pH-responsive nano-carrier was designed for co-delivery of Doxorubicin hydrochloride (DOX) and Hydroxytyrosol (HT) in HT-29 colon cancer cells. For this purpose, Poly (lactide-co-glycolic acid-co-acrylic acid) (PLGA-co-PAA) was synthesized by radical AA telomerization in the presence of mercaptoethanol (ME), followed by the ring-opening polymerization (ROP) of lactide and glycolide in the presence of PAA-OH as a chain transfer agent. Nanoparticles with homogeneous spherical morphology and an average diameter of around 18 nm were obtained; cellular uptake of DOX@HT-loaded nanoparticles was more than 94%. Cell cycle analysis and DAPI staining results revealed a high amount of apoptosis on HT-29 cancer cells treated with the dual drug-loaded nanoparticles in comparison to free drugs and single drug-loaded nano-formulations. RT-PCR analysis indicated that the expression levels of hTERT, CREB1 and CREB2 genes were significantly down-regulated in the presence of nano-encapsulated drugs versus free drugs in the HT-29 cell line. Moreover, results revealed that DOX@HT NPs inhibited gene expression more efficiently than single forms. All these results confirmed that these pH-responsive biodegradable nanoparticles are suitable for combination chemotherapy and further in vivo studies in future.
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