Tumor-targeted hyaluronic acid-mPEG modified nanostructured lipid carriers for cantharidin delivery: An in vivo and in vitro study
| Autor: | Yuyan Guo, Eryu Shang, Shuang Sun, Shaowa Lv, Aixia Ju, Qian Wu, Yalun Li, Yang Yang, Dayu Yang, Qiu-Hong Li |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Pharmacology environment and public health Polyethylene Glycols Rats Sprague-Dawley Mice chemistry.chemical_compound Pharmacokinetics Oral administration In vivo Cell Line Tumor Drug Discovery Hyaluronic acid Animals Hyaluronic Acid Cytotoxicity Mice Inbred BALB C Cantharidin Molecular Structure Liver Neoplasms fungi General Medicine Lipids enzymes and coenzymes (carbohydrates) chemistry Toxicity health occupations Female CTD Nanoparticle Drug Delivery System |
| Zdroj: | Fitoterapia. 155:105033 |
| ISSN: | 0367-326X |
| Popis: | Aim Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial. Methods A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm. Results Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%. Conclusions Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy. |
| Databáze: | OpenAIRE |
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