Biodegradable Polymersomes as Nanocarriers for Doxorubicin Hydrochloride: Enhanced Cytotoxicity in MCF-7/ADR Cells and Prolonged Blood Circulation

• Published in: Pharmaceutical research 2017-03, Vol.34 (3), p.610-618
• Main Authors: Chao, Yanhui, Liang, Yuheng, Fang, Guihua, He, Haibing, Yao, Qing, Xu, Hang, Chen, Yinrong, Tang, Xing
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Biochemistry; Biodegradation; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood; Cancer; Care and treatment; Cell Line, Tumor; Cell Survival; Cells; Chloride; Circulatory system; Cytotoxicity; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - blood; Doxorubicin - chemistry; Doxorubicin - toxicity; Drug Liberation; Drug resistance; Drug Resistance, Multiple; Ethylene glycol; Ethylene Glycols - chemistry; Half-Life; Humans; Hydrophobic and Hydrophilic Interactions; Male; Medical Law; Nanocapsules - chemistry; Pharmacology/Toxicology; Pharmacy; Polyesters - chemistry; Rats, Sprague-Dawley; Research Paper
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-016-2088-9

Purpose DOX is one of the most potent anticancer drugs. But its short half-life and the occurrence of multi-drug resistance (MDR) markedly limit its clinical application. To solve these problems, we develop DOX loaded polymersomes (DOX polymersomes). Methods An methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-b-PCL) copolymer was synthesized and used to prepare DOX polymersomes. The pharmaceutical properties of DOX polymersomes were characterized. The in vitro release profile of DOX from polymersomes was investigated. The in vitro cytotoxicity and cell uptake studies were performed on MCF-7 and MCF-7/ADR cells. The in vivo pharmacokinetic profiles were investigated on Sprague–Dawley rats. Results DOX polymersomes had a nano-scale particle size of about 60 nm with a hydrophobic membrane about 10 nm in thickness. Release of DOX from the polymersomes took place in a sustained manner. Cell experiments showed DOX polymersomes enhanced the cytotoxicity and the intracellular accumulation of DOX in MCF-7/ADR cells, compared with free DOX. In vivo pharmacokinetic study showed the DOX polymersomes increased the bioavailability and prolonged the circulation time in rats. Conclusions The entrapment of DOX in biodegradable polymersomes could enhance cytotoxicity in MCF-7/ADR cells and improve its in vivo pharmacokinetic profile.