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| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Wang X. Yang L. Hong J. Di J. Guo Y. Han M. Liu M. |
| Abstract | Linjie Yang,1 Jingyi Hong,1 Jing Di,1 Yifei Guo,1 Meihua Han,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG1000-HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG1000-HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC50 value against HepG2 cells and 14.1 times lower IC50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG1000-HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy. Keywords: 10-hydroxycamptothecin, nanosuspensions, stabilizer, antitumor efficacy |
| e-ISSN | 11782013 |
| Journal | International Journal of Nanomedicine |
| Volume Number | 12 |
| Language | English |
| Publisher | Dove Medical Press |
| Publisher Date | 2017-01-01 |
| Publisher Place | United Kingdom |
| Access Restriction | Open |
| Subject Keyword | Medicine (general) Stabilizer Antitumor Efficacy 10-hydroxycamptothecin Nanosuspensions |
| Content Type | Text |
| Resource Type | Article |
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