Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment Marcio A. C. da Silva, 1 Renata N. Oliveira, 1 Roberta Helena Mendonc¸a, 2 Talita G. B. Lourenc ¸o, 3 Ana Paula V. Colombo, 3 Marcelo N. Tanaka, 4 Elena M. O. Tude, 4 Marysilvia F. da Costa, 1 Rossana Mara S. M. Thir e 1 1 COPPE/Program of Metallurgical and Materials Engineering, Federal University of Rio de Janeiro, Rio de Janeiro City, Rio de Janeiro, Brazil 2 Chemical Engineering Department of the Technology Institute, Federal Rural University of Rio de Janeiro, Rio de Janeiro City, Rio de Janeiro, Brazil 3 Institute of Microbiology Paulo de G oes, Centre of Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro City, Rio de Janeiro, Brazil 4 Bioceramics and Cell Culture Lab, Brazilian Center for Physics Research, Rio de Janeiro City, Rio de Janeiro, Brazil Received 30 July 2014; revised 23 October 2014; accepted 9 December 2014 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33357 Abstract: Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3- hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3- hydroxybutyrate) membranes containing 0.5–2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick’s law. Membranes were noncytotoxic. The amount of met- ronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the mem- branes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4. V C 2015 Wiley Periodi- cals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2015. Key Words: poly(3-hydroxybutyrate), drug delivery/release, antimicrobial, periodontitis, guided tissue regeneration (GTR) How to cite this article: da Silva MAC, Oliveira RN, Helena Mendonc ¸a R, Lourenc ¸o TGB, Colombo APV, Tanaka MN, Tude EMO, da Costa MF, Thir e RMSM. 2015. Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment. J Biomed Mater Res Part B 2015:00B:000–000. INTRODUCTION Periodontitis is the inflammation of periodontal tissues that support the teeth. It is the most common type of inflamma- tion found in humans, and 86% of adults over the age of 70 had at least one case of moderate periodontitis, leading to the loss of teeth in 25% of the cases. 1–3 With the progres- sion of the periodontitis disease, a periodontal pocket is developed. Periodontal pockets are a pathological deepening of the gingival sulcus, and its first signal is the accumulation of plaque around the teeth. 4 Among the micro-organisms present in the periodontal pockets, Porphyromonas gingiva- lis is an anaerobic gram-negative bacterium and an impor- tant etiologic agent of periodontal disease. The proliferation of micro-organisms leads to tissue injury and the P. gingiva- lis specifically acts in the deregulated immune and inflam- matory systems of the body. 5 Different strategies of periodontal therapy aim to reduce or eliminate the effects caused by the plaque in the peri- odontal tissues and to regenerate new periodontal tissues. The treatment is based on the removal of the etiologic agents. 3,6,7 Guided tissue regeneration (GTR), a technique based on placing a barrier membrane between the tooth and the gingival tissue to prevent epithelial growth in the wound site, which allows the formation of functional struc- tures, can be used for periodontium reconstruction. 3,8 There are two types of membranes applied to GTR: the bioresorbable ones and the nonresorbable ones. The main nonresorbable membranes for the GTR application are: (i) Correspondence to: R. M. S. M. Thir e; e-mail: rossana@metalmat.ufrj.br Contract grant sponsor: CNPq Contract grant sponsor: CAPES Contract grant sponsor: FAPERJ V C 2015 WILEY PERIODICALS, INC. 1