a ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility , University of Wollongong , Wollongong , Australia.
b Utrecht University , Utrecht , The Netherlands.
Expert Opin Drug Deliv. 2018 Sep;15(9):915-925. doi: 10.1080/17425247.2018.1517745. Epub 2018 Sep 12.
Epilepsy is a chronic brain disease characterized by unprovoked seizures, which can have severe consequences including loss of awareness and death. Currently, 30% of epileptic patients do not receive adequate seizure alleviation from oral routes of medication. Over the last decade, local drug delivery to the focal area of the brain where the seizure originates has emerged as a potential alternative and may be achieved through the fabrication of drug-loaded polymeric implants for controlled on-site delivery.
This review presents an overview of the latest advanced fabrication techniques for controlled drug delivery systems for refractory epilepsy treatment. Recent advances in the different techniques are highlighted and the limitations of the respective techniques are discussed.
Advances in biofabrication technologies are expected to enable a new paradigm of local drug delivery systems through offering high versatility in controlling drug release profiles, personalized customization and multi-drug incorporation. Tackling some of the current issues with advanced fabrication methods, including adhering to GMP-standards and industrial scale-up, together with innovative solutions for complex designs will see to the maturation of these techniques and result in increased clinical research into implant-based epilepsy treatment.
GMP: Good manufacturing process; DDS(s): Drug delivery system(s); 3D: Three-dimensional; AEDs: Anti-epileptic drugs; BBB: Blood brain barrier; PLA: Polylactic acid; PLGA: Poly(lactic-co-glycolic acid); PCL: poly(ɛ-caprolactone); ESE: Emulsification solvent evaporation; O/W: Oil-in-water; W/O/W: Water-in-oil-in-water; DZP: Diazepam; PHT: Phenytoin; PHBV: Poly(hydroxybutyrate-hydroxyvalerate); PEG: Polyethylene glycol; SWD: Spike-and-wave discharges; CAD: Computer aided design; FDM: Fused deposition modeling; ABS: Acrylonitrile butadiene styren; eEVA: Ethylene-vinyl acetate; GelMA: Gelatin methacrylate; PVA: Poly-vinyl alcohol; PDMS: Polydimethylsiloxane; SLA: Stereolithography; SLS: Selective laser sintering.
癫痫是一种慢性脑部疾病,其特征是无诱因发作,可导致意识丧失和死亡等严重后果。目前,30%的癫痫患者无法通过口服药物途径得到充分的癫痫缓解。在过去的十年中,针对癫痫起源的脑局灶部位的局部药物递送已成为一种潜在的替代方法,可通过制备载药聚合物植入物以实现现场控制递药来实现。
本综述介绍了用于治疗耐药性癫痫的控释药物递送系统的最新先进制造技术概述。强调了不同技术的最新进展,并讨论了各自技术的局限性。
生物制造技术的进步有望通过控制药物释放曲线、个性化定制和多药物结合提供高度的多功能性,从而实现局部药物递送系统的新模式。解决先进制造方法的一些当前问题,包括符合 GMP 标准和工业规模扩大,以及为复杂设计提供创新解决方案,将使这些技术成熟,并增加基于植入物的癫痫治疗的临床研究。
GMP:良好生产规范;DDS(s):药物递送系统(s);3D:三维;AEDs:抗癫痫药物;BBB:血脑屏障;PLA:聚乳酸;PLGA:聚(乳酸-共-羟基乙酸);PCL:聚(ε-己内酯);ESE:乳化溶剂蒸发;O/W:油包水;W/O/W:水包油包水;DZP:地西泮;PHT:苯妥英钠;PHBV:聚(羟基丁酸酯-羟基戊酸酯);PEG:聚乙二醇;SWD:棘波和尖波放电;CAD:计算机辅助设计;FDM:熔融沉积建模;ABS:丙烯腈-丁二烯-苯乙烯;eEVA:乙烯-醋酸乙烯酯共聚物;GelMA:明胶甲基丙烯酸盐;PVA:聚乙烯醇;PDMS:聚二甲基硅氧烷;SLA:立体光刻;SLS:选择性激光烧结。