Master of Philosophy
Intelligent Polymer Research Institute
Epilepsy is the most prevalent chronic brain disease affecting approximately 1% of the worldwide population. Systemic treatment with anti-epileptic drugs are reported to only control seizures in up to 70% of the patients, while the remaining patients report insufficient seizure alleviation. Due to drug resistance, an increasing concentration of the drug is required for systemic administration, resulting in pronounced side effects. Localized drug delivery in the form of an implant enabling sustained drugrelease is regarded as a promising strategy to challenge refractory epilepsy.
Collagen, a naturally derived polymer, is one of the most useful biomaterials which has been widely used in medical applications. Recently, an electrochemical technique has been developed to generate oriented and highly clustered collagen fibres with increased mechanical stiffness. The objective of this study was to investigate the potential to incorporate drug-loaded microspheres into electrochemical compacted collagen (ECC) with a view to achieve a sustained dual drug-release profile. Dexamethasone (DEX), commonly used to prevent acute inflammatory reactions after implantation, and phenytoin (PHT), an anti-epileptic drug, were encapsulated into poly (lactic-co-glycolic) acid microspheres via emulsification solvent evaporation technique. Sphere-loaded ECC membranes were successfully prepared by suspension of the microspheres into the collagen solution prior to the electrochemical compaction process. Tensile tests revealed that the incorporation of microspheres decreases the tensile strength of ECC membranes by 25% from 1.11 ± 0.36 MPa to 0.73 ± 0.24 MPa. Finally, the drug-release behaviour of sphere-loaded ECC membranes were investigated in an in-vitro experiment. Invitro release studies of DEX-MP/PHT-MP loaded ECC matrices showed DEX-elution to reduce from 86% to 60% of completion at day 11, whereas PHT-elution was characterized by a high burst release resulting in PHT-elution increased from 4% to 82% of completion at day 1.
In conclusion, the incorporation of drug-loaded microspheres into ECC membranes demonstrates a promising approach for the development of novel collagen-based drug delivery systems with increased mechanical properties. The data indicates that sustained drug release from ECC matrices highly depends on the ability of the targeted drug to undergo the electrochemical fabrication process and thus further studies need to be performed in order to receive an in-depth understanding of the procedure.
Berthel, Marius, Dual Drug-eluting Collagen Matrix for Epilepsy Treatment, Master of Philosophy thesis, Intelligent Polymer Research Institute, University of Wollongong, 2019. https://ro.uow.edu.au/theses1/753
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.