730 Macromolecular Research, Vol. 18, No. 8, pp 730-736 (2010) www.springer.com/13233 The Polymer Society of Korea Self-Assembly of Negatively Charged Poly(vinyl alcohol) Derivatives Paramee Jitjumnong 1,2 , Supason P. Wanichwecharungruang 1, *, and Sunatda Arayachukeat 2 1 Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand 2 National Center of Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Bangkok 10330, Thailand Received December 21, 2009; Revised April 29, 2010; Accepted April 29, 2010 Abstract: This paper reports the relationship between the degree of negatively charged groups on the poly(4-viny- loxybutane sulfonate-co-vinyl alcohol) or PVA-BS and poly(4-vinyloxybutane sulfonate-co-vinyloxydodecane-co- vinyl alcohol) or PVA-12C-BS polymers and their self-assembled particles’ morphologies. With grafted hydropho- bic moieties (PVA-12C-BS polymers), the size of the self-assembled particles decreased with increasing levels of butane sulfonate substitution. However, with no hydrophobic moiety grafted (PVA-BS), the size of the self-assem- bled particles increased with increasing levels of butane sulfonate substitution. The response of the PVA-BS and PVA-12C-BS polymeric particles to the loading of a model hydrophobic compound, 2-ethylhexyl-4-methoxycin- namate (EHMC), was markedly different. With the drug as a hydrophobic core, EHMC-loaded PVA-BS particles were smaller in size and more stable than the unloaded particles. In contrast, the EHMC-loaded PVA-12C-BS par- ticles were larger than the corresponding unloaded particles. Keywords: poly(vinyl alcohol), negatively charged particle, butane sulfonate, self-assembly. Introduction Poly(vinyl alcohol) (PVA or PVOH) is a hydrophilic poly- mer that is biodegradable, biocompatible, nontoxic, non- carcinogenic and can be eliminated from the human body by renal excretion. Thus, it is a well accepted ‘pharmaceuti- cally safe’ polymer for both humans and the environment, and as such has been used in various pharmaceutical, medi- cal, cosmetic, food and agricultural products. 1 In the area of drug delivery, PVA is commonly used as an emulsion stabi- lizer in the preparation of nanoparticles, 2-4 coating of parti- cles, 5,6 and as a starting material to prepare hydrogels, 7 micelles and polymeric micro/nanoparticles. In addition, the prepara- tion of cationic spheres based on either a blend of PVA and polyethylenimine with poly(D,L-lactide-co-glycolide), 8 or melamine formaldehyde particles coated with chitosan- PVA-borate gel, 9 have also been reported. Reports on the use of PVA as the main polymeric carrier include the use of PVA hydrogel nanoparticles, prepared by water-in-oil emulsification plus repeating freezing-thawing process for protein/peptide drug delivery, 10 PVA-DNA nanoparticles, prepared by ultra high pressure technology for gene delivery, 11 PVA-poly(vinyl pyrrolidone) nanoparti- cles, 12 and crosslinked PVA hydrogels. 13,14 Indeed, the Ori- enti team and some other research groups have prepared various PVA derivatives for use as drug carriers. Most of the reported PVA derivatives have been prepared by grafting the appropriate functional chemical moieties, such as vari- ous acyl chains, 15,16 functional 2-hydroxypropyltrimethyl- ammonium derivatives, 7 triethylene glycol monoethyl ether, 17 tetraethylene glycol monoethyl ether, 18 functional amine derivatives, 19 amino/poly(D,L-lactide-co-glycolide), 20 oleyl amine, 21 various cinnamoyl derivatives, 22 and sulfobutyl/ poly(lactide-co-glycolide), 23 onto the PVA backbone. Amongst these, PVA grafted with functional 2-hydroxypropyltrimeth- ylammonium or amino groups possess positive charge char- acteristics, while those grafted with sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide)s provides negative charges. Within the limited number of available reports on the neg- atively charged polymers, a relationship between a number of negative charges on the polymer and its self-assembled morphology has never been reported. In this work, thus, several derivatives of the negatively charged poly(4-vinyl- oxybutane sulfonate-co-vinyl alcohol), or PVA-BS, and poly (4-vinyloxybutane sulfonate-co-vinyloxydodecane-co-vinyl alcohol), or PVA-12C-BS, with various degrees of substitu- tion of either the dodecane or the butane sulfonate moieties on the PVA backbone, were prepared and allowed to self- assemble into nanospheres. The correlation between the morphology of the particles and the polymer structure is discussed. In addition, loading of the model hydrophobic compound, 2-ethylhexyl-4-methoxycinnamate, into the nano- spheres was also evaluated and is discussed. DOI 10.1007/s13233-010-0816-2 *Corresponding Author. E-mail: psupason@chula.ac.th