Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic drug delivery, part 2: in vitro and in vivo toxicity evaluation

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology 2011-02, Vol.13 (2), p.721-731
• Main Authors: Gong, ChangYang, Wang, YuJun, Wang, XiuHong, Wei, XiaWei, Wu, QinJie, Wang, BiLan, Dong, PengWei, Chen, LiJuan, Luo, Feng, Qian, ZhiYong
• Format: Article
• Language: English
• Subjects: Acute toxicity; Biodegradation; Body weight; Characterization and Evaluation of Materials; Chemistry and Materials Science; Cytotoxicity; Inorganic Chemistry; Intravenous administration; Lasers; Materials Science; Nanoparticles; Nanotechnology; Optical Devices; Optics; Photonics; Physical Chemistry; Research Paper; Zeta potential
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-010-0071-7

Polymeric micelles, prepared by self-assembly of biodegradable poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG–PCL–PEG, PECE) copolymer in aqueous solution, were proved to be a potential carrier for hydrophobic drug honokiol in our previous contribution. In this study, the safety of blank PECE micelles was evaluated in vitro and in vivo before its further application in biomedical field. The average particle size of obtained micelle was 83.47 ± 0.44 nm, and polydisperse index was 0.27 ± 0.01. Also, the zeta potential of prepared micelles was about −0.41 ± 0.02 mV. Otherwise, cytotoxicity of PECE micelles was evaluated by cell viability assay using L929 cells, and in vitro hemolytic test was also performed. In vivo acute toxicity evaluation and histopathological study of PECE micelles were conducted in BALB/c mice by intravenous administration. Furthermore, serum chemistry profile and complete blood count test were performed. In acute toxicity test, the mice were observed continuously for 7 days. For histopathological study, samples including heart, liver, spleen, lung, and kidneys were histochemical prepared and stained with hematoxylin-eosin (H&E). No mortality or significant signs of acute toxicity was observed during the whole observation period, and there is no significant lesion to be shown in histopathological study of major organs. The maximal tolerance dose of PECE micelles (100 mg/mL) by intravenous administration was calculated to be higher than 10 g/kg body weight (b.w.). The results indicated that the obtained PECE micelles was non-toxic after intravenous administration, and could be a safe candidate for hydrophobic drug delivery system.