Doxorubicin Loading and In Vitro Release from Poly(alkylcyanoacrylate) Nanoparticles Produced by Redox Radical Emulsion Polymerization Khairallah Alhareth, 1,2 Christine Vauthier, 2 Claire Gueutin, 1,2 Gilles Ponchel, 1,2 Fathi Moussa 3 1 Univ Paris-Sud, Physico-chimie, Pharmacotechnie, Biopharmacie, UMR 8612, Chatenay-Malabry, F-92296 2 CNRS, Chatenay-Malabry, F-92296 3 Universite ´ Paris Sud, LETIAM, IUT d’Orsay, plateau de Moulon, Ba ˆtiment 602, 91400 Orsay, France Received 3 March 2010; accepted 9 May 2010 DOI 10.1002/app.32789 Published online 27 July 2010 in Wiley Online Library (wileyonlinelibrary.com). ABSTRACT: The aim of this work was to explore the capacity to load an anticancer agent Doxorubicin (Dox) on new poly(alkylcyanoacrylate) (PACA) nanoparticles pre- pared by redox radical emulsion polymerization (RREP). These nanoparticles present several advantages compared with the previously described PACA nanoparticles obtained by anionic emulsion polymerization (AEP). Their cytotoxicity was lower and because they do not activate the complement system, they are believed to behave like stealth nanoparticles after intravenous administration. Dox was incorporated during the preparation of the nanopar- ticles. However, the drug molecules were degraded by ce- rium IV, which is a strong oxidant agent. To avoid drug degradation, Dox must be loaded by adsorption on pre- formed nanoparticles. Optimal loading capacity was deduced from a Scatchard’s analysis of the Dox adsorption pattern. The loading performance [Loading efficiency (LE) 74%, Loading content (LC) 3.7%], the Dox release and the amount of Dox retained by the new nanoparticles 75% were similar to those of the already well described PACA nanoparticles obtained by AEP (LE 79% and LC 4.2%, drug retention capacity 75%). It can be concluded that the loading and releasing properties make the new nanopar- ticles an interesting carrier candidate for the in vivo deliv- ery of Dox. V C 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 816–822, 2011 Key words: nanoparticles; poly(alkylcyanoacrylate); doxorubicin; drug delivery system; redox radical; emulsion polymerization INTRODUCTION Many types of nanoparticles have been designed as drug carriers with the objective of optimizing the delivery of active molecules in vivo, hence improving the therapeutic index of the drug. Poly(alkylcyano- acrylate) (PACA) nanoparticles are considered as the most promising biodegradable polymeric drug car- riers for drug targeting. 1–4 The first PACA nanopar- ticles were prepared by anionic emulsion polymer- ization of alkylcyanoacrylate in the presence of dextran (AEP-PACA). 5 They were reported to accu- mulate massively in the liver and the spleen a few minutes after intravenous administration. 6–8 As nanoparticle interactions with circulating proteins and nanoparticle biodistribution depend on their surface properties, 9–12 a new method of synthesis of PACA nanoparticles by redox radical emulsion poly- merization (RREP) was developed in our labora- tory. 13,14 The surface of RREP-PACA nanoparticles can be modulated by the nature, and the molecular weight of the polysaccharide used as stabilizer of the polymer colloids. More interestingly, the poly- saccharide chain conformation stranded at the nano- particle surface was modified with the new method of polymerization. 15 This discrete modification of the structure of the nanoparticle polysaccharide coating induced a dramatic change of the nanoparticle prop- erties when they are brought in contact with biologi- cal systems. For instance, the cytotoxicity of the new nanoparticles was reduced by a factor of 20 com- pared with that of the AEP-PACA nanoparticles. 16 The capacity of the new nanoparticles to activate the complement system was low and opposite to that shown by AEP-PACA nanoparticles. 17 With such a low capacity of complement activation, it is believed that the new nanoparticles are a good candidate to be stealth after intravenous administration, whereas the AEP nanoparticles are massively taken up by the macrophages of the reticulo-endothelial system. 18 Another advantage is found in the method of prepa- ration, which provides with a nanoparticle suspen- sion 10 times more concentrated than a suspension obtained by the AEP method. Thus, it will not be necessary to concentrate the nanoparticle suspension prior to in vivo administration, as it is often the case Correspondence to: C. Vauthier (christine.vauthier@ u-psud.fr) or F. Moussa (fathi.maussa@u-psud.fr). Journal of Applied Polymer Science, Vol. 119, 816–822 (2011) V C 2010 Wiley Periodicals, Inc.