Valproate release from polycaprolactone implants prepared by 3D-bioplotting

In this study we examined the release kinetics of valproate from polycaprolactone (PCL) implants constructed for local antiepileptic therapy. The PCL implants were produced with a novel 3D-Bioplotting technology. Release kinetics were determined by superfusion of these implants. Valproate was measured in the superfusate fractions with high pressure liquid chromatography (HPLC). The HPLC measurements were linear over a concentration range of 10-500 g/mL for valproate and the limit of quantification was found to be 9 g/mL. The HPLC method used is simple, accurate and sensitive. Within the first day, valproate (10%w/w)-PCL implants released already 77% of the maximum possible liberated amount whereas (5%w/w)-PCL implants released only 53%. After four days, 88% of valproate was released from (10%w/w)-PCL implants and 94% valproate from (5%w/w)-PCL implants. When valproate was ground before the 3D-Bioplotting process, only 63% from (10%w/w)-PCL implants was released within the first day. This released amount of ground valproate was significantly lower compared to that which was not ground from the (10%w/w)-PCL implants. After three days of superfusion a total amount of 89% of ground valproate within the implants was released, corresponding to 88% of non-ground valproate after four days. The fast releasing PCL implants can be used to study acute effects of locally applied valproate on epileptogenesis in vivo after initiation of an epileptic focus in an animal model. The corresponding biocompatibility may also be analysed.