Rabin C, Liang Y, Ehrlichman R S, Budhian A, Metzger K L, Majewski-Tiedeken C, Winey K I, Siegel S J
Stanley Center for Experimental Therapeutics, Division of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, United States.
Schizophr Res. 2008 Jan;98(1-3):66-78. doi: 10.1016/j.schres.2007.08.003. Epub 2007 Aug 31.
Non-adherence with medication is a critical limitation in current long-term treatment of schizophrenia and a primary factor in poor quality-of-life outcomes. However, few treatments have addressed this shortcoming using an implantable drug delivery approach. The goal of this study was to provide in vitro and in vivo proof of concept for a long-term implantable risperidone delivery system in mice.
Implantable formulations of risperidone were created using the biodegradable polymer Poly Lactic co Glycolic Acid (PLGA) combined with various drug loads. Implant bioactivity was tested using in vitro release and stability studies, as well as in vivo pharmacokinetic and behavioral studies in mice.
The pattern of risperidone release is influenced by various parameters, including polymer composition and drug load. In vitro measures demonstrate that risperidone is stable in implants under physiological conditions. Behavioral measures demonstrate the bioactivity of risperidone implants delivering 3 mg/kg/day in mice, while pharmacokinetic analyses indicate that reversibility is maintained throughout the delivery interval.
The current report suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications based on in vivo animal studies and pharmacokinetics. Implantable medications demonstrated here can last two months or longer while maintaining coherence and removability past full release, suggesting a potential paradigm shift in the long-term treatment of schizophrenia.
药物依从性差是当前精神分裂症长期治疗的关键限制因素，也是生活质量不佳的主要因素。然而，很少有治疗方法采用可植入药物递送方法来解决这一缺点。本研究的目的是为小鼠体内的长效可植入利培酮递送系统提供体外和体内概念验证。
使用可生物降解聚合物聚乳酸-乙醇酸共聚物（PLGA）结合不同药物载量制备利培酮的可植入制剂。通过体外释放和稳定性研究以及小鼠体内药代动力学和行为学研究来测试植入物的生物活性。
利培酮的释放模式受多种参数影响，包括聚合物组成和药物载量。体外测量表明，利培酮在生理条件下在植入物中是稳定的。行为学测量表明，在小鼠中递送3mg/kg/天的利培酮植入物具有生物活性，而药代动力学分析表明在整个递送间隔期内保持可逆性。
本报告表明，基于体内动物研究和药代动力学，可植入制剂是提供抗精神病药物长期递送的可行方法。此处展示的可植入药物可持续两个月或更长时间，同时在完全释放后保持连贯性和可移除性，这表明精神分裂症的长期治疗可能会发生范式转变。
