Emulsion-coaxial electrospinning: designing novel architectures for sustained release of highly soluble low molecular weight drugs Lucie Viry, a Simon E. Moulton, * a Tony Romeo, a Courtney Suhr, b Damia Mawad, a Mark Cook bc and Gordon G. Wallace a Received 21st February 2012, Accepted 10th April 2012 DOI: 10.1039/c2jm31069d In drug therapy, most therapeutic drugs are of low molecular weight and could freely diffuse in the biological milieu depending on the administration route applied. The main reason for the development of polymeric drug carriers is to obtain desired effects such as sustained therapy, local and controlled release, prolonged activity and reduction of side effects. Alternatively, polymeric carriers can be made bioerodible in order to be eliminated by natural ways after a certain time of therapy. Core–shell ﬁbres from coaxial spinneret or emulsion electrospinning are good candidates for the development of such devices; however difﬁculties remain especially in controlling the release over a sustained period. Here, we present a novel technique combining coaxial and emulsion electrospinning to produce micro- structured core–shell ﬁbres. The design of drug microreservoirs of variable size within the bulk of the ﬁbre combined with a tailored diffusive barrier allows modulating the release kinetics of these novel carriers. A nearly constant and linear release of the model drug Levetiracetam (M w z 170 g mol 1 ) from PLGA emulsion-coaxial electrospun ﬁbres is observed over 20 days. This device is aimed to be implanted into the brain for the treatment of epilepsy and is an example of the new capabilities and the promising potential that emulsion-coaxial electrospinning can provide towards the development of future drug carriers. Introduction Among several methods for preparing bioactive loaded polymer structures for drug delivery, the electrospinning technique pres- ents a number of advantages, in particular, the possibility to fabricate high speciﬁc surface area structures in a facile approach requiring mild preparation. 1 Electrospun ﬁbres have been successfully developed for the encapsulation and the delivery of bioactive compounds within the body for therapeutic treat- ments. 2–20 Whatever the route of delivery, the polymeric device is usually required to release the drug with zero-order kinetics. 21 In the quest to produce a delivery device which has appropriate kinetics, a number of strategies have been developed including controlled erosion of the surface of the polymeric carrier loaded with a drug. 4,10,22,23 In these devices the rate of erosion has to be faster than the rate of drug diffusion, and the penetration of a solvent front into the polymer should be constant. 15,24–26 Zero order kinetics implies a homogeneous drug distribution and a release proﬁle governed by the wetting properties of the material. Nevertheless, some issues remain, especially concerning the encapsulation of highly hydrophilic and neutrally charged drugs of low molecular weight. 12,27–29 The interaction of these types of molecules with the polymer is usually very poor and their rate of diffusion is often faster than the rate of polymer erosion. This fast rate of diffusion has detrimental effects on drug release from electrospun polymer structures. Typically drug enrichment at the surface of electrospun ﬁbres occurs when the drug is blended into a polymer solution prior to electrospinning, and results in a severe burst release phenomenon. 30 This burst release reduces the effective lifetime of the delivery device. Finding ways to regulate encapsulation efﬁciency and thus release proﬁles would greatly add to the inventory of strategies available for designing sustained delivery systems. A simple approach is to create a membrane-reservoir device in which an excess of the drug is surrounded by a rate-controlling membrane. Signiﬁcant interest towards the fabrication of core–shell ﬁbrous structures for biomedical applications has led to the development of coaxial electrospinning. 3,31 A coaxial dual-capillary spinneret, whereby a capillary is surrounded by a larger one (Fig. 1A), has been employed in electrospinning to fabricate core–sheath structures providing a more effective method of encapsulation for bioactive additives and hence providing a suitable drug a ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, University of Wollongong, Northﬁelds Avenue, Wollongong, NSW, 2522, Australia. E-mail: smoulton@uow. edu.au b Clinical Neurosciences, St. Vincent’s Hospital, 5th Floor, Daly Wing, 35 Victoria Parade, Fitzroy, Victoria 3065, Australia c Department of Medicine, University of Melbourne, St. Vincent’s Hospital, 35 Victoria Parade, Fitzroy, Victoria 3065, Australia This journal is ª The Royal Society of Chemistry 2012 J. Mater. Chem., 2012, 22, 11347–11353 | 11347 Dynamic Article Links C < Journal of Materials Chemistry Cite this: J. Mater. Chem., 2012, 22, 11347 www.rsc.org/materials PAPER Downloaded by The University of Melbourne Libraries on 19 March 2013 Published on 04 May 2012 on http://pubs.rsc.org | doi:10.1039/C2JM31069D View Article Online / Journal Homepage / Table of Contents for this issue