International Journal of Pharmaceutics 381 (2009) 1–18 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Historical Perspectives Biodegradable poly(-caprolactone)–poly(ethylene glycol) copolymers as drug delivery system XiaWei Wei a,b , ChangYang Gong a , MaLing Gou a , ShaoZhi Fu a , QingFa Guo a , Shuai Shi a , Feng Luo a , Gang Guo a , LiYan Qiu b , ZhiYong Qian a, a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China b College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China article info Article history: Received 20 March 2009 Received in revised form 25 July 2009 Accepted 29 July 2009 Available online 5 August 2009 Keywords: Poly(-caprolactone)–poly(ethylene glycol) copolymer Microparticles Nanoparticles Polymeric drug delivery systems Hydrogels abstract Poly(-caprolactone)–poly(ethylene glycol) (PCL–PEG) copolymers are important synthetic biomedical materials with amphiphilicity, controlled biodegradability, and great biocompatibility. They have great potential application in the fields of nanotechnology, tissue engineering, pharmaceutics, and medicinal chemistry. This review introduced several aspects of PCL–PEG copolymers, including synthetic chemistry, PCL–PEG micro/nanoparticles, PCL–PEG hydrogels, and physicochemical and toxicological properties. © 2009 Elsevier B.V. All rights reserved. Contents 1. Introduction .......................................................................................................................................... 2 2. PCL/PEG copolymers ................................................................................................................................. 2 2.1. Synthesis of PCL/PEG copolymers ............................................................................................................ 2 2.1.1. Synthesis of PCL/PEG diblock copolymers .......................................................................................... 2 2.1.2. The synthesis of PCL–PEG-PCL and PEG-PCL–PEG triblock copolymers ........................................................... 3 2.1.3. Synthesis of PCL/PEG star-shaped copolymers ..................................................................................... 3 2.2. The biocompatibility of PCL/PEG copolymers ................................................................................................ 3 2.3. The degradation of PCL/PEG copolymers ..................................................................................................... 4 3. PCL/PEG micro/nanoparticles ........................................................................................................................ 5 3.1. Preparation of drug-loaded micro/nanoparticles based on PCL/PEG copolymers ........................................................... 5 3.1.1. Emulsion solvent extraction method ............................................................................................... 5 3.1.2. Dialysis method ..................................................................................................................... 6 3.1.3. Spray-drying method ............................................................................................................... 7 3.1.4. Others ............................................................................................................................... 7 3.2. Application of micro/nanoparticles .......................................................................................................... 7 3.2.1. Delivery of small molecular drugs .................................................................................................. 7 3.2.2. Delivery of biomacromolecules .................................................................................................... 9 4. PCL/PEG hydrogel .................................................................................................................................... 10 4.1. Introduction of PCL–PEG hydrogel ........................................................................................................... 10 4.2. Thermosensitive hydrogels .................................................................................................................. 11 Corresponding author. Tel.: +86 28 85164063; fax: +86 28 85164060. E-mail address: anderson-qian@163.com (Z. Qian). 0378-5173/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2009.07.033