title: Cationic gemini surfactant as a dual linker for a cholic acid-modified polysaccharide in aqueous solution: thermodynamics of interaction and phase behavior.
abstract: Understanding the thermodynamics of formation of biocompatible aggregates is a key factor in the bottom up approach to the development of novel types of drug carriers and their structural tuning using small amphiphilic molecules. We chose an anionic amphiphilic and biocompatible polymer that consists of a dextran and grafted cholic acid pendants, randomly distributed along the dextran backbone, with a degree of substitution (DS) of 15 mol% (designated Dex-15CACOONa). The thermodynamics of interaction and phase behavior of mixtures of this polyelectrolyte and a cationic gemini surfactant hexanediyl-α,ω-bis(dodecyldimethylammonium bromide) (C12C6C12Br2) or its monomer surfactant dodecyltrimethylammonium bromide (DTAB) in aqueous solution were characterized by isothermal titration calorimetry (ITC) and turbidity, together with cryogenic transmission electron microscopy (Cryo-TEM). The various critical concentrations and the enthalpy changes of the corresponding phase transitions for the oppositely charged system were obtained from the plots of the observed enthalpy change (ΔHobs) and turbidity measurements as a function of gemini concentration. The morphologies of the aggregates in various phases were observed by Cryo-TEM. Altogether these results suggest the critical role of gemini as a dual linker. At the concentrations where the crosslink between the pendant aggregates happens, the free gemini concentration is proximately zero and the aggregate retains its negative charge. The analysis of various factors involved in the interaction allowed a rationalization of the driving forces for mixed aggregate formation, which will contribute to a subsequent rational design of drug delivery systems based on this polymer/surfactant system.
authors.affiliation: Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. baiguangyue@htu.cn.
authors.forename: Guangyue
authors.initials: G
authors.lastname: Bai
authors.affiliation: Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. baiguangyue@htu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. baiguangyue@htu.cn.
authors.forename: Pengxiao
authors.initials: P
authors.lastname: Lou
authors.affiliation: School of Chemistry and Chemical Engineering, Henan Institute of Science and Technology, Xinxiang, Henan 453003, P. R. China. yujiewang2001@163.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iasi, Romania. nichifor@icmpp.ro.
authors.forename: Marieta
authors.initials: M
authors.lastname: Nichifor
authors.affiliation: Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. baiguangyue@htu.cn.
authors.forename: Kelei
authors.initials: K
authors.lastname: Zhuo
authors.affiliation: Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China. baiguangyue@htu.cn.
authors.forename: Jianji
authors.initials: J
authors.lastname: Wang
authors.affiliation: CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre, 687, P-4169-007 Porto, Portugal. mbastos@fc.up.pt.
authors.forename: Margarida
authors.identifier: http://orcid.org/0000-0001-7464-3568
authors.initials: M
authors.lastname: Bastos
mesh_terms: D019826:Cholic Acid / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D011134:Polysaccharides / Q000737:chemistry* / Q000648:ultrastructure; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D011134:Polysaccharides; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D014867:Water; D019826:Cholic Acid; C022806:dodecyltrimethylammonium