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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doaj-cc5038a3fea847febeb20f1ec73838a92020-11-25T02:53:11ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642017-01-0124183484510.1080/10717544.2017.13265401326540Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2Peng Li0XiaoYue Zhou1Ding Qu2Mengfei Guo3Chenyi Fan4Tong Zhou5Yang Ling6Changzhou Cancer Hospital of Soochow UniversityChangzhou Cancer Hospital of Soochow UniversityAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineChangzhou Cancer Hospital of Soochow UniversityChangzhou Cancer Hospital of Soochow UniversityThe 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.http://dx.doi.org/10.1080/10717544.2017.1326540celastrolginsenoside rh2micelleanti-lung cancerdrug release |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peng Li XiaoYue Zhou Ding Qu Mengfei Guo Chenyi Fan Tong Zhou Yang Ling |
spellingShingle |
Peng Li XiaoYue Zhou Ding Qu Mengfei Guo Chenyi Fan Tong Zhou Yang Ling Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 Drug Delivery celastrol ginsenoside rh2 micelle anti-lung cancer drug release |
author_facet |
Peng Li XiaoYue Zhou Ding Qu Mengfei Guo Chenyi Fan Tong Zhou Yang Ling |
author_sort |
Peng Li |
title |
Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 |
title_short |
Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 |
title_full |
Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 |
title_fullStr |
Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 |
title_full_unstemmed |
Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside Rh2 |
title_sort |
preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol–polyethylene glycol–ginsenoside rh2 |
publisher |
Taylor & Francis Group |
series |
Drug Delivery |
issn |
1071-7544 1521-0464 |
publishDate |
2017-01-01 |
description |
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. |
topic |
celastrol ginsenoside rh2 micelle anti-lung cancer drug release |
url |
http://dx.doi.org/10.1080/10717544.2017.1326540 |
work_keys_str_mv |
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