Surgically implantable long-term antipsychotic delivery systems for the treatment of schizophrenia.
Non-adherence with medication remains a major correctable cause for poor outcome in schizophrenia. We describe a surgically implantable preparation of haloperidol with the aim that patients will have superior outcomes with improved medication adherence from implants. In contrast to depot formulations, implantable pellets could last many months, providing symptomatic improvement for periods of time never before possible. Additionally, in the event of unacceptable side effects, implants could be removed, offering a degree of reversibility not available with depot formulations. A surgically-implantable formulation of haloperidol has been created using biodegradable polymers. Implants have been characterized for in-vitro kinetics, as well as in-vivo bioactivity in rodents. Haloperidol implants demonstrate steady release of drug for 5 months. Animals treated with haloperidol implants display increased striatal D2 receptor expression as well as increased apomorphine stimulated locomotion. Surgically-implantable formulations are a viable approach to provide long-term delivery of antipsychotic medications to patients with psychotic disorders.
Siegel
Steven J
SJ
Division of Neuropsychiatry, Laboratory of Molecular Neuropsychopharmacolgy, Stanley Center for Experimental Therapeutics, University of Pennsylvania, Gates Building 10th floor, 3400 Spruce Street, Philadelphia, PA 19104, USA. siegels@mail.med.upenn.edu
Winey
Karen I
KI
Gur
Raquel E
RE
Lenox
Robert H
RH
Bilker
Warren B
WB
Ikeda
Debbie
D
Gandhi
Neel
N
Zhang
Wen-Xiao
WX
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D002408:Catheters, Indwelling / Q000706:statistics & numerical data; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D006220:Haloperidol / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011098:Polyglactin 910 / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D017448:Receptors, Dopamine D2; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D006220:Haloperidol