Research paper Development of microporous drug-releasing films cast from artificial nanosized latexes of poly(styrene-co-methyl methacrylate) or poly(styrene-co-ethyl methacrylate) Daniel P. Otto a,b, * , Hermanus C.M. Vosloo c , Wilna Liebenberg b , Melgardt M. de Villiers a a School of Pharmacy, University of Wisconsin – Madison, WI, USA b Faculty of Health Sciences, North-West University, Potchefstroom, South Africa c School of Chemistry, North-West University, Potchefstroom, South Africa Received 10 November 2007; accepted in revised form 1 February 2008 Available online 14 February 2008 Abstract Two sets of copolymers comprising of styrene and either methyl or ethyl methacrylate as comonomer were conveniently synthesized by microemulsion copolymerization. The purified materials were characterized by GPC-MALLS and were shown to form artificial nan- olatexes in THF. ATR-FTIR analysis revealed differences in copolymer composition and based on the copolymer properties, a selection of copolymers was chosen to cast drug-loaded, microporous films that exhibit microencapsulation of drug agglomerates. The contact angles of the copolymers suggested potential applications in medical devices to prevent the formation of bacterial biofilms that com- monly result in infections. Additionally, the different copolymeric films showed two phases of drug release characterized by a rapid initial drug release followed by a zero-order phase. Depending on the application, one could select the copolymer films that best suited the application i.e. for short-term drug release applications such as urinary catheters or long-term applications such as artificial implants. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Methacrylate copolymer; Microencapsulation; Film; Rifampin; Controlled release 1. Introduction Several studies have reported the introduction of infec- tions in patients which received polymer-based medical devices, i.e. orthopedic surgical implants [1], urinary cathe- ters [2], cardiovascular stents [3] and ventilator-associated pneumonia with use of endotracheal tubes [4]. The proce- dures associated with the use of these devices are invasive and compromise natural barriers of the body that protect it from infection [5]. In the event of bacterial accumulation, a so-called biofilm is created on a surface, i.e. a polymer film or coating. This biofilm is often a very resistant and physically strong struc- ture comprising several stacked layers of microorganisms [6]. Once the biofilm has been established the onset of an infection could be observed. Therefore, the development of strategies to curb infections associated with the use of poly- meric devices is warranted if the devices should actually ben- efit, not compromise, the health of patients [7,8] Circumvention of biofilm formation could entail a num- ber of approaches. Some techniques modify the surface chemistry of the polymer film to hinder bacterial attachment by methods such as thiocyanation since thiol groups could be microbiocidal [9]. Other methods employ loading the poly- mer device with antimicrobial agents, i.e. rifampin, fusidic acid and mupirocin combinations [10], rifampin and mino- cycline [11], gentamicin [12,13], vancomycin [14] and cipro- floxacin [15] that release low quantities of the drugs over prolonged periods that effectively eradicate the biofilm. Several tests could be conducted to establish the surface properties and the contact angle of the polymer film could 0939-6411/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2008.02.004 * Corresponding author. School of Pharmacy, University of Wisconsin – Madison, 777 Highland Avenue, Madison, WI 53705, USA. Tel.: +1 608 262 9351. E-mail address: dotto@wisc.edu (D.P. Otto). www.elsevier.com/locate/ejpb Available online at www.sciencedirect.com European Journal of Pharmaceutics and Biopharmaceutics 69 (2008) 1121–1134