International Journal of Pharmaceutics 448 (2013) 71–78 Contents lists available at SciVerse ScienceDirect International Journal of Pharmaceutics jo ur nal homep a ge: www.elsevier.com/locate/ijpharm Pharmaceutical nanotechnology Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials Todsapon Nitanan, Prasert Akkaramongkolporn, Theerasak Rojanarata, Tanasait Ngawhirunpat, Praneet Opanasopit ∗ Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand a r t i c l e i n f o Article history: Received 8 October 2012 Received in revised form 26 January 2013 Accepted 10 March 2013 Available online xxx Keywords: Neomycin Poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) Polyvinyl alcohol (PVA) Ion exchange fiber Electrospinning a b s t r a c t In this study, poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) blended with polyvinyl alcohol (PVA) was electrospun and then subjected to thermal crosslinking to produce PSSA-MA/PVA ion exchange nanofiber mats. The cationic drug neomycin (0.001, 0.01, and 0.1%, w/v) was loaded onto the cationic exchange fibers. The amount of neomycin loaded and released and the cytotoxicity of the fiber mats were analyzed. In vivo wound healing tests were also performed in Wistar rats. The results indicated that the diameters of the fibers were on the nanoscale (250 ± 21 nm). The ion exchange capacity (IEC) value and the percentage of water uptake were 2.19 ± 0.1 mequiv./g-dry fibers and 268 ± 15%, respectively. The loading capacity was increased upon increasing the neomycin concentration. An initial concentration of 0.1% (w/v) neomycin (F3) showed the highest loading capacity (65.7 mg/g-dry fibers). The neomycin- loaded nanofiber mats demonstrated satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria, and an in vivo wound healing test revealed that these mats performed better than gauze and blank nanofiber mats in decreasing acute wound size during the first week after tissue damage. In conclusion, the antibacterial neomycin-loaded PSSA-MA/PVA cationic exchange nanofiber mats have the potential for use as wound dressing materials. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Pharmaceutical applications of ion exchange resins are exten- sively focused in drug delivery systems, such as controlled release, taste masking, site specific and topical delivery systems [Anand et al., 2001]. Recently, ion exchange fibers have been increas- ingly studied due to the many advantages of these mats over ion exchange resins, such as the easier incorporation of large molecules, more efficient drug loading onto and release from the ion exchange fibers and more rapid and efficient ion-exchange per- formance [Hänninen, 2008]. There are only a few studies reporting the pharmaceutical use of ion exchange fibers, such as in transder- mal delivery systems [Jaskari et al., 2000] and gastro-mucoadhesive delivery systems [Yao et al., 2008] to control drug release and per- meation and to improve drug absorption and stability. Ion exchange fibers consist of polymeric frameworks and ion exchange groups. Polymeric frameworks are produced primarily in nanofiber form due to the notable characteristics of nanofibers, which include a very large surface-to-volume ratio, a high porosity ∗ Corresponding author. Tel.: +66 34 255800; fax: +66 34 250941. E-mail addresses: praneet@su.ac.th, opraneet@hotmail.com (P. Opanasopit). with a small pore size and good mechanical properties. The addi- tion of ionic functional groups into the nanofibers is a promising option to produce novel ion exchangers with high exchange capac- ities [Matsumoto and Tanioka, 2011]. Electrospinning is a popular technique used to create nanofibers because it is a simple and easy way to control the morphology of ultrafine fibers [Huang et al., 2003; Bhardwaj and Kundu, 2010; Sill and von Recum, 2008]. Two approaches are applied to produce ion-exchange nanofibers. In one approach, electrospinnable polymers, such as polyvinyl alcohol (PVA) [Matsumoto et al., 2007] and polyethylene oxide (PEO) [Seo et al., 2005], are added to the spinning solution of an ionic polymer with a high electric conductivity that acts as the carrier because of the low electrospinnability of ionic polymer solutions. In the sec- ond approach, nonionic polymers are electrospun and subjected to successive chemical modification (sulfonation [Matsumoto et al., 2006] or amination [Park and Na, 2006]) to create ion exchange groups. Recently, ionic polymers such as chitosan [Matsumoto et al., 2007] and polysaccharide [Seo et al., 2005] have been used in the preparation of ion exchange fibers, whereas poly(styrene sulfonic acid) (PSSH), poly(sodium styrene sulfonate) (PSSNa), poly(acrylic acid) (PAA), poly(dimethyl dimethylenepiperidinum chloride) (PDMeDMPCl) [Matsuyama et al., 2001], poly(acrylic acid- co-maleic acid) (PAM) [Kim et al., 2005] and poly(styrene sulfonic 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.03.011