Carbohydrate Polymers 113 (2014) 304–313 Contents lists available at ScienceDirect Carbohydrate Polymers j ourna l ho me pa g e: www.elsevier.com/locate/carbpol In vitro and in vivo evaluation of chitosan microspheres with different deacetylation degree as potential embolic agent Xuan Zhou a,b,∗∗,1 , Ming Kong a , Xiao Jie Cheng a , Chao Feng a , Jing Li a , Jing Jing Li c , Xi Guang Chen a,∗,1 a College of Marine Life Science, Ocean University of China, Qingdao 266003, China b Key Laboratory for Nano-Bio Interface Research, Suzhou Key Laboratory for Nanotheranostics, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China c College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022, China a r t i c l e i n f o Article history: Received 15 May 2014 Received in revised form 15 June 2014 Accepted 20 June 2014 Available online 11 July 2014 Keywords: Chitosan Microspheres Transcatheter arterial embolization Embolic agent Chemoembilization a b s t r a c t To evaluate the potential of N-acetylated chitosan microspheres used as a chemoembolic agent in vivo and in vitro. Calibrated spherical chitosan microspheres (CMs) were prepared via Water-in-Oil emul- sification method and CMs were acetylated (ACMs). The swelling rate of CMs was greatly affected by pH than that of ACMs and both of them affected by temperature. Microspheres with excellent thermal stability demonstrated controllable degradation in lysozyme solution. Doxorubicin was released from microspheres in vitro and exhibited excellent control release profile. ACMs caused hemolysis less than CMs (<5% of the time). Co-culture with mouse embryo fibroblasts revealed that microspheres have non- cytotoxic nature. Microspheres planted in a rat gluteal muscle demonstrated that it were biodegradable and biocompatible. ACMs were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular occlusion after 15 days. Acetylated chitosan microspheres could be used as potential biocompatible and biodegradable embolic agents. © 2014 Published by Elsevier Ltd. 1. Introduction Transcatheter arterial embolization (TAE) is widely employed for clinical interventional therapy, which embolic agents are introduced into the blood vessel through a catheter with a min- imally invasive procedure (Oerlemans et al., 2013; Sharafuddin, Sun, & Golzarian, 2006; Weng, Rostamzadeh, Nooryshokry, Le, & Golzarian, 2013). The embolic agents cut off the nutrition and oxygen supply necessary of organ, tissue or tumor by blocking the blood flow, and it can be used in the treatment of many diseases, including hemorrhagic syndrome, vascular lesions and ∗ Corresponding author at: College of Marine Life Science, Ocean University of China, 5# Yushan Road, Qingdao 266003, China. Tel.: +86 0532 82032586; fax: +86 0532 82032586. ∗∗ Corresponding author at: Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, 398# Ruoshui Road, Suzhou Industrial Park, Suzhou 215123, China. Tel.: +86 0512 62872646. E-mail addresses: zhouxuan1008@163.com (X. Zhou), xgchen@ouc.edu.cn (X.G. Chen). 1 These authors contributed equally to this manuscript as co-corresponding authors. tumors (Ginat, Saad, & Turba, 2009). These embolic agents such as coils, liquid, gelfoam and particles have been researched and most of them are permanent or nonocclusive (Schwarz, Zhang, Metcalfe, Salazkin, & Raymond, 2004). In the early years, Gelfoam, a com- mercially available biodegradable embolic agent, has been already applied in clinic. It has non-spherical surface and it is difficult to precisely calibrate for embolization because of fast degrada- tion. In addition, polyvinyl alcohol (PVA) microspheres used as non-biodegradable materials are regarded as permanent embolic agents, but PVA particles with irregular shapes cannot be cali- brated and tend to aggregate, which causes catheter obstruction and large vessel occlusion (Derdeyn, Moran, Cross, Dietrich, & Dacey, 1995). In present years, only a few types of microspheres are commercially available, i.e., tris-acryl microspheres (Embo- sphere; Biosphere Medical, Roissy, France), Contour SE (CSE; Target Therapeutics, Boston Scientific Corp., Fremont CA, USA) and Bead Block (DC-bead, Biocompatible Ltd., UK) (Kwak, Shim, Han, & Park, 2005). It seems that they could be used selectively for embolization although each of them has advantages and disadvantages. There- fore, it is crucial to explore a new type of microspheres, including calibrated particle size, non-aggregate, degradation and biocom- patibility, which are ideal material for embolization (Jayakrishnan et al., 1994). http://dx.doi.org/10.1016/j.carbpol.2014.06.080 0144-8617/© 2014 Published by Elsevier Ltd.