Journal
PHARMACEUTICAL RESEARCH
Volume 37, Issue 7, Pages -Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-020-02819-7
Keywords
combination chemotherapy; dihydroartemisinin; nanoparticle; paclitaxel; PEGylated
Funding
- Vietnam National Foundation for Science and Technology Development (NAFOSTED) [108.05-2017.300]
- National Research Foundation of Korea [22A20154413174] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Purpose Development of a nanoplatform constructed by the PEG-dual drug conjugation for co-delivery of paclitaxel (PTX) and Dihydroartemisinin (DHA) to the tumor. Methods PEG was conjugated with PTX and DHA to form PTX-PEG-DHA complex as a nanocarrier. The PTX and DHA were co-encapsulated in PTX-PEG-DHA nanoparticles (PD@PPD NPs) by the emulsion evaporation method. The physicochemical properties of PD@PPD Nps were characterized, including size, zeta potential, and morphology. The drug loading capacity and entrapment efficiency,in vitrodrug release at different pH conditions were also evaluated. Forin vitroassessment, the effects of the NPs on HT-29 colorectal cancer cells, including intracellular uptake, cytotoxicity, and Bcl-2 protein expression were assessed. Thein vivodistribution of the NPs was investigated by labelling the NPs with Cyanine 5.5 fluorophore. Finally, the antitumor efficacy of the NPs was evaluated in HT-29 tumor-bearing mice. Results The nanoparticles were formed at small size (similar to 114 nm) and narrow distribution. The combination of PTX and DHA in the DHA-PEG-PTX nanosystems (PD@PPD) showed remarkably increased apoptosis in colorectal adenocarcinoma HT-29 cells, as compared to free drug treatment. More importantly, the PD@PPD nanoparticles exhibited significantly higher accumulation in the tumor site owing to the enhanced permeability and retention (EPR) effect, effectively restrained the tumor growthin vivoat low-dose of PTX while reducing the systemic toxicity. Conclusions The combination of PTX and DHA in a PEG-conjugated dual-drug co-delivery system can minimize the severe side effect associated with the high-dose of PTX while enhancing the antitumor efficacy.
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