Kammerer M, Fabritius M, Carvalho C, Mülhaupt R, Feuerstein T J, Trittler R
Section of Clinical Neuropharmacology, Department of Neurosurgery, Albert-Ludwigs University, Freiburg, Germany.
Pharmazie. 2011 Jul;66(7):511-6.
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 microg/mL for valproate and the limit of quantification was found to be 9 microg/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.
在本研究中，我们检测了用于局部抗癫痫治疗的聚己内酯（PCL）植入物中丙戊酸盐的释放动力学。PCL植入物采用新型3D生物打印技术制造。通过对这些植入物进行超灌流来测定释放动力学。用高压液相色谱法（HPLC）测定超灌流液组分中的丙戊酸盐。丙戊酸盐在10 - 500μg/mL浓度范围内，HPLC测量呈线性，定量限为9μg/mL。所采用的HPLC方法简便、准确且灵敏。在第一天内，含10%（重量/重量）丙戊酸盐的PCL植入物已释放出最大可能释放量的77%，而含5%（重量/重量）丙戊酸盐的PCL植入物仅释放了53%。四天后，含10%（重量/重量）丙戊酸盐的PCL植入物释放了88%的丙戊酸盐，含5%（重量/重量）丙戊酸盐的PCL植入物释放了94%的丙戊酸盐。当丙戊酸盐在3D生物打印过程之前进行研磨时，含10%（重量/重量）丙戊酸盐的PCL植入物在第一天内仅释放了63%。与未研磨的含10%（重量/重量）丙戊酸盐的PCL植入物相比，研磨后的丙戊酸盐释放量明显更低。超灌流三天后，植入物中研磨后的丙戊酸盐总量释放了89%，相当于未研磨的丙戊酸盐四天后的释放量88%。快速释放的PCL植入物可用于研究在动物模型中癫痫病灶形成后，局部应用丙戊酸盐对体内癫痫发生的急性影响。相应的生物相容性也可进行分析。
