Carbohydrate Polymers 92 (2013) 691–696 Contents lists available at SciVerse ScienceDirect Carbohydrate Polymers jo u rn al hom epa ge: www.elsevier.com/locate/carbpol Short communication Comb-like ionic complexes of hyaluronic acid with alkyltrimethylammonium surfactants Ainhoa Tolentino, Abdelilah Alla, Antxon Martínez de Ilarduya, Sebastián Mu˜ noz-Guerra ∗ Department d’Enginyeria Química, Universitat Politècnica de Catalunya, ETSEIB, Diagonal 647, Barcelona 08028, Spain a r t i c l e i n f o Article history: Received 5 August 2012 Received in revised form 12 September 2012 Accepted 22 September 2012 Available online 28 September 2012 Keywords: Ionic polymer complex Comb-like polymer Hyaluronic acid Polyuronic acid Surfactant polyuronic complex a b s t r a c t Stoichiometric complexes of hyaluronic acid with alkyltrimethylammonium surfactants bearing octa- decyl, eicosyl and docosyl groups were prepared by ionic coupling in aqueous solution. The complexes were non soluble in water but soluble in organic solvents. In the solid state they self-assembled in a biphasic layered structure with the alkyl side chains forming a separate phase that melted in the 50–60 ◦ C range. They were stable to heating up to above 200 ◦ C. © 2012 Elsevier Ltd. All rights reserved. 1. Introduction Hyaluronic acid (HyalA) is a linear polysaccharide ubiquitous in the human body. It is composed of repeating disaccharide units of -1,3-N-acetyl glucosamine and -1,4-glucuronic acid with a molecular weight up to 6 million Da. With excellent viscoelasti- city, high moisture retention capacity, high biocompatibility and non-immunogenicity, HyalA finds a wide-range of applications in surgery, cosmetology, veterinary science, and hygiene medicine, where it has been used for over 30 years (Kogan, Soltes, Stern, & Gemeiner, 2007; Necas, Bartosikova, Brauner, & Kolar, 2008). When chemically modified by reaction of the pendant reactive groups, HyalA can be transformed into a variety of new biomaterials with properties suitable for tissue repair and regeneration (Allison & Grande-Allen, 2006; Burdick & Prestwich, 2011; Schante, Zuber, Herlin, & Vandamme, 2011). HyalA has been recently explored for its use in novel drug delivery systems with increasing enthusiasm because HyalA-binding receptors are believed to be involved in cancer metastasis (Yadav, Mishra, & Agrawal, 2008). Traditionally HyalA was extracted from rooster combs but now it is increasingly produced through microbial fermentation, which has enhanced its application interest and commercial value (Izawa et al., 2009; Liu, Liu, Li, Du, & Chen, 2011). ∗ Corresponding author. Tel.: +34 934016680; fax: +34 934017150. E-mail address: sebastian.munoz@upc.edu (S. Mu˜ noz-Guerra). In these last years it has been revealed that coupling of polyelectrolytes with ionic surfactants is a convenient method for the preparation of ionic complexes with remarkable struc- ture and properties (Macknight, Ponomarenko, & Tirrell, 1998; Ponomarenko, Waddon, Tirrell, & Macknight, 1996). Specifically, coupling of polyacids with tetraalkylammonium surfactants bear- ing long alkyl chains is known to lead to amphiphilic comb-like systems displaying a layered biphasic structure (Fig. 1a) able to lodge agents with chemical or biomedical activity (Portilla-Arias, García-Alvarez, Martínez de Ilarduya, Holler, & Mu˜ noz-Guerra, 2006a, 2006b; Pérez-Camero et al., 2004; Portilla-Arias, García- Alvarez, Martínez de Ilarduya, & Mu˜ noz-Guerra, 2007a). In this communication we wish to report on the preparation, struc- ture and thermal behavior of complexes made of hyaluronic acid with alkyltrimethylammonium surfactants, abbreviated as nATMA·HyalA, with alkyl chains containing 18, 20 and 22 carbon atoms (Fig. 1b). Recently we have reported on similar complexes made of polyuronic acids (nATMA·PUR), specifically, polygalac- turonic and alginic acids (Tolentino, Alla, Martínez de Ilarduya, & Mu˜ noz-Guerra, 2011; Tolentino, Martínez de Ilarduya, Alla, & Mu˜ noz-Guerra, 2010) and the binding of certain amphiphilic drugs to HyalA was investigated with regards to the flexibility of the polyanion (Caram-Lelham, Hed, & Sundelöf, 1997). The choice of HyalA as polyacid made in this work obeys to two reasons, to extend the ionic coupling method to this polysaccharide in order to broaden its potential as biomaterial, and to appraise how the alter- nating ionic structure of Hyal may affect the formation of these comb-like ionic complexes. 0144-8617/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.carbpol.2012.09.042