title: A novel enzymatically-mediated drug delivery carrier for bone tissue engineering applications: combining biodegradable starch-based microparticles and differentiation agents.
abstract: In many biomedical applications, the performance of biomaterials depends largely on their degradation behavior. For instance, in drug delivery applications, the polymeric carrier should degrade under physiological conditions slowly releasing the encapsulated drug. The aim of this work was, therefore, to develop an enzymatic-mediated degradation carrier system for the delivery of differentiation agents to be used in bone tissue engineering applications. For that, a polymeric blend of starch with polycaprolactone (SPCL) was used to produce a microparticle carrier for the controlled release of dexamethasone (DEX). In order to investigate the effect of enzymes on the degradation behavior of the developed system and release profile of the encapsulated osteogenic agent (DEX), the microparticles were incubated in phosphate buffer solution in the presence of alpha-amylase and/or lipase enzymes (at physiological concentrations), at 37 degrees C for different periods of time. The degradation was followed by gravimetric measurements, scanning electron microscopy (SEM) and Fourier transformed infrared (FTIR) spectroscopy and the release of DEX was monitored by high performance liquid chromatography (HPLC). The developed microparticles were shown to be susceptible to enzymatic degradation, as observed by an increase in weight loss and porosity with degradation time when compared with control samples (incubation in buffer only). For longer degradation times, the diameter of the microparticles decreased significantly and a highly porous matrix was obtained. The in vitro release studies showed a sustained release pattern with 48% of the encapsulated drug being released for a period of 30 days. As the degradation proceeds, it is expected that the remaining encapsulated drug will be completely released as a consequence of an increasingly permeable matrix and faster diffusion of the drug. Cytocompatibility results indicated the possibility of the developed microparticles to be used as biomaterial due to their reduced cytotoxic effects.
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. erosado@dep.uminho.pt
authors.forename: Elizabeth Rosado
authors.initials: ER
authors.lastname: Balmayor
authors.forename: Kadriye
authors.initials: K
authors.lastname: Tuzlakoglu
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Marques
authors.forename: Helena S
authors.initials: HS
authors.lastname: Azevedo
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
mesh_terms: D001673:Biodegradation, Environmental; D002454:Cell Differentiation; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013213:Starch / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D000516:alpha-Amylases / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D003907:Dexamethasone; D013213:Starch; D000516:alpha-Amylases