Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems 英文参考文献.docVIP

Polymers 2011, 3, 779-811; doi:10.3390/polym3020779 OPEN ACCESS polymers ISSN 2073-4360 /journal/polymers Review Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems Giulia Bonacucina, Marco Cespi, Giovanna Mencarelli, Gianfabio Giorgioni and Giovanni Filippo Palmieri * School of Pharmacy, University of Camerino, Via S. Agostino 1, I-62032 Camerino (MC), Italy; E-Mails: giulia.bonacucina@unicam.it (G.B.); marco.cespi@unicam.it (M.C.); giovanna.mencarelli@unicam.it (G.M.); gianfabio.giorgioni@unicam.it (G.G.) * Author to whom correspondence should be addressed; E-Mail: gianfilippo.palmieri@unicam.it; Tel.: +39-0737402289; Fax: +39-0737637345. Received: 28 February 2011; in revised form: 23 March 2011 / Accepted: 11 April 2011 / Published: 19 April 2011 Abstract: Self-assembling block copolymers (poloxamers, PEG/PLA and PEG/PLGA diblock and triblock copolymers, PEG/polycaprolactone, polyether modified poly(Acrylic Acid)) with large solubility difference between hydrophilic and hydrophobic moieties have the property of forming temperature dependent micellar aggregates and, after a further temperature increase, of gellifying due to micelle aggregation or packing. This property enables drugs to be mixed in the sol state at room temperature then the solution can be injected into a target tissue, forming a gel depot in-situ at body temperature with the goal of providing drug release control. The presence of micellar structures that give rise to thermoreversible gels, characterized by low toxicity and mucomimetic properties, makes this delivery system capable of solubilizing water-insoluble or poorly soluble drugs and of protecting labile molecules such as proteins and peptide drugs. Keywords: self-assembling; block copolymers; sol-gel; thermogel; drug delivery 1. Introduction Amphiphilic block copolymers (AB or ABA-type) with large solubility differences between hydrophilic and hydr