Presence of starch enhances in vitro biodegradation and biocompatibility of a gentamicin delivery formulation Elizabeth R. Balmayor, 1,2 * Turker E. Baran, 1,2 Marina Unger, 3 Alexandra P. Marques, 1,2 Helena S. Azevedo, 1,2 Rui L. Reis 1,2 1 3B’s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimar~ aes, Portugal 2 IBB – Institute for Biotechnology and Bioengineering, PT Associated Laboratory, AvePark, 4806-909 Taipas, Guimar~ aes, Portugal 3 Department of Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, D-81675 Munich, Germany Received 16 June 2014; revised 17 October 2014; accepted 18 November 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33343 Abstract: The effect of a-amylase degradation on the release of gentamicin from starch-conjugated chitosan microparticles was investigated up to 60 days. Scanning electron micro- scopic observations showed an increase in the porosity and surface roughness of the microparticles as well as reduced diameters. This was confirmed by 67% weight loss of the microparticles in the presence of a-amylase. Over time, a highly porous matrix was obtained leading to increased per- meability and increased water uptake with possible diffusion of gentamicin. Indeed, a faster release of gentamicin was observed with a-amylase. Starch-conjugated chitosan par- ticles are non-toxic and highly biocompatible for an osteo- blast (SaOs-2) and fibroblast (L929) cell line as well as adipose-derived stem cells. When differently produced starch-conjugated chitosan particles were tested, their cyto- toxic effect on SaOs-2 cells was found to be dependent on the crosslinking agent and on the amount of starch used. V C 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Bio- mater 00B: 000–000, 2014. Key Words: starch-conjugated chitosan, gentamicin, micro- particles, enzymatic degradation, cytotoxicity How to cite this article: Balmayor ER, Baran TE, Unger M, Marques AP, Azevedo HS, Reis RL. 2014. Presence of starch enhances in vitro biodegradation and biocompatibility of a gentamicin delivery formulation. J Biomed Mater Res Part B 2014:00B:000–000. INTRODUCTION Biomaterials with the ability to perform certain medical functions and subsequently degrade are of great importance. Their degradation should occur under a controlled mecha- nism and into easily metabolized products. 1,2 Among the well-known advantages of using biodegradable materials are the elimination of the long-term presence of foreign materi- als and the consequent need for a second surgery for implant removal. 1 Several definitions for biodegradability have been pro- posed. 1,3,4 In the context of biomedical applications, biode- gradation may be defined as the “gradual breakdown of a material mediated by a specific biological activity.” 4 When in contact with tissues, biomaterials start to degrade as a result of their interaction with biological environments. Their stability will define their application in clinics. In drug delivery applications, biodegradability of the carrier system affects and finally controls the release kinetics of the encap- sulated drugs. 5 Thus, the polymeric carriers should degrade under physiological conditions allowing for the gradual release of the entrapped drug as well as facilitate repeating dosages to ensure successful treatments. 6,7 At this point, a major concern related to biodegradable polymers is the pos- sible toxicity of the leachable molecules and degradation products derived from the material processing and degrada- tion. 8 Thus, the nature of the materials to be selected as drug delivery carriers is also a rather important factor to consider. Polysaccharides are very attractive in this respect as the degradation process results in nontoxic end products such as glucose, maltose, and oligosaccharides. These end products may even be incorporated in the normal metabolic pathways of the human body. 1,9 Chitosan and starch have been extensively employed as a carrier in drug delivery systems. 9–13 Both natural poly- mers are biocompatible and biodegradable. 9 In particular, starch is a cheap, abundant and edible polysaccharide with Correspondence to: E. R. Balmayor; e-mail: elizabeth.rosado-balmayor@tum.de *Present address: Clinic for Plastic Surgery and Hand Surgery, Technical University Munich, Ismaninger Strasse 22, 81675 Munich, Germany Contract grant sponsor: Marie Curie Alea Jacta EST; contract grant number: MEST-CT-2004-008104 Contract grant sponsor: European NoE EXPERTISSUES; contract grant number: NMP3-CT-2004-500283 V C 2014 WILEY PERIODICALS, INC. 1