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...
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Book |
Published: |
Taylor & Francis Group,
2017-01-01T00:00:00Z.
|
Subjects: | |
Online Access: | Connect to this object online. |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
LEADER | 00000 am a22000003u 4500 | ||
---|---|---|---|
001 | doaj_cc5038a3fea847febeb20f1ec73838a9 | ||
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. |