In Vitro and In Vivo Safety Evaluation of Biodegradable Self-Assembled Monomethyl Poly (Ethylene Glycol)–Poly(ε-Caprolactone)–Poly (Trimethylene Carbonate) Micelles

Safety evaluation of self-assembled polymeric micelles is important for biomedical involvement in drug delivery systems in the future. In this study, biodegradable monomethyl poly (ethylene glycol)–poly (e-caprolactone)–poly (trimethylene carbonate) [MPEG–P(CL-co-TMC)] copolymer was synthesized and characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis, and gel permeation chromatography. MPEG–P(CL-co-TMC) micelles were prepared by self-assembly without any organic solvent. The present study was conducted to assess the safety of blank MPEG–P(CL-co-TMC) micelles both in vitro and in vivo. Particle size (30.09 ± 0.06 nm) and zeta potential (0.067 ± 0.027 mV) of obtained micelles were determined by Malvern laser particle size analyzer. The results of in vitro toxicity evaluation implied that the prepared micelles did not cause hemolysis or severely cell toxicity. Meanwhile, we did not observe any toxic response or histopathological changes in the study of in vivo acute toxicity evaluation and histopathological study of MPEG–P(CL-co-TMC) micelles. In conclusion, the maximal tolerance dose of MPEG–P(CL-co-TMC) micelles (100 mg/mL) by intravenous injection was supposed to be greater than 10 g/kg body weight. Therefore, it might have potential applications in biomedical field. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:305–313, 2014