Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol-polyethylene glycol-ginsenoside Rh2

The aim of this study was to develop an amphipathic polyethylene glycol (PEG) derivative that was bi-terminally modified with celastrol and ginsenoside Rh2 (Celastrol-PEG-G Rh2). Such derivative was capable of forming novel, celastrol-loaded polymeric micelles (CG-M) for endo/lysosomal delivery and...

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Main Authors: Peng Li (Author), XiaoYue Zhou (Author), Ding Qu (Author), Mengfei Guo (Author), Chenyi Fan (Author), Tong Zhou (Author), Yang Ling (Author)
Format: Book
Published: Taylor & Francis Group, 2017-01-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Peng Li  |e author 
700 1 0 |a XiaoYue Zhou  |e author 
700 1 0 |a Ding Qu  |e author 
700 1 0 |a Mengfei Guo  |e author 
700 1 0 |a Chenyi Fan  |e author 
700 1 0 |a Tong Zhou  |e author 
700 1 0 |a Yang Ling  |e author 
245 0 0 |a Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol-polyethylene glycol-ginsenoside Rh2 
260 |b Taylor & Francis Group,   |c 2017-01-01T00:00:00Z. 
500 |a 1071-7544 
500 |a 1521-0464 
500 |a 10.1080/10717544.2017.1326540 
520 |a The aim of this study was to develop an amphipathic polyethylene glycol (PEG) derivative that was bi-terminally modified with celastrol and ginsenoside Rh2 (Celastrol-PEG-G Rh2). Such derivative was capable of forming novel, celastrol-loaded polymeric micelles (CG-M) for endo/lysosomal delivery and thereby synergistic treatment of lung cancer. Celastrol-PEG-G Rh2 with a yield of 55.6% was first synthesized and characterized. Its critical micellar concentration was 1 × 10−5 M, determined by pyrene entrapment method. CG-M had a small particle size of 121.53 ± 2.35 nm, a narrow polydispersity index of 0.214 ± 0.001 and a moderately negative zeta potential of -23.14 ± 3.15 mV. Celastrol and G Rh2 were rapidly released from CG-M under acidic and enzymatic conditions, but slowly released in normal physiological environments. In cellular studies, the internalization of celastrol and G Rh2 by human non-small cell lung cancer (A549) cells treated with CG-M was 5.8-fold and 1.8-fold higher than that of non-micelle control. Combinational therapy of celastrol and G Rh2 using CG-M exhibited synergistic anticancer activities in cell apoptosis and proliferation assays via rapid drug release within endo/lysosomes. Most importantly, the celastrol in CG-M exhibited a long elimination half-life of 445.3 ± 43.5 min and an improved area under the curve of 645060.8 ± 63640.7 ng/mL/h, that were 1.03-fold and 2.44-fold greater than those of non-micelle control, respectively. These findings suggest that CG-M is a promising vector for precisely releasing anticancer drugs within the tumor cells, and thereby exerts an improved synergistic anti-lung cancer effect. 
546 |a EN 
690 |a celastrol 
690 |a ginsenoside rh2 
690 |a micelle 
690 |a anti-lung cancer 
690 |a drug release 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Drug Delivery, Vol 24, Iss 1, Pp 834-845 (2017) 
787 0 |n http://dx.doi.org/10.1080/10717544.2017.1326540 
787 0 |n https://doaj.org/toc/1071-7544 
787 0 |n https://doaj.org/toc/1521-0464 
856 4 1 |u https://doaj.org/article/cc5038a3fea847febeb20f1ec73838a9  |z Connect to this object online.