Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
Department of Chemical Engineering, McMaster University, Hamilton, Canada.
Eur J Pharm Biopharm. 2014 May;87(1):30-9. doi: 10.1016/j.ejpb.2014.02.007. Epub 2014 Feb 18.
Lectin-functionalized, polyethylene glycol-block-poly-(D,L)-lactic-co-glycolic acid nanoparticles loaded with haloperidol were prepared with narrow size distributions and sizes <135nm. The nanoparticles exhibited high Solanum tuberosum lectin (STL) conjugation efficiencies, encapsulation efficiencies, and drug loading capacities. The in vitro release of haloperidol was 6-8% of the loaded amount in endo-lysosomal conditions over 96h, demonstrating minimal drug leakage and the potential for the efficient drug transport to the targeted brain tissue. The haloperidol released upon erosion was successful in displacing [(3)H] N-propylnorapomorphine and binding to bovine striatal dopamine D2 receptors. Both haloperidol-loaded nanoparticle formulations were found to be highly effective at inducing catalepsy. Intranasal administration of STL-functionalized nanoparticles increased the brain tissue haloperidol concentrations by 1.5-3-fold compared to non-STL-functionalized particles and other routes of administration. This formulation demonstrates promise in the reduction of the drug dose necessary to produce a therapeutic effect with antipsychotic drugs for the treatment of schizophrenia.
用凝集素功能化的聚乙二醇嵌段聚（D，L）-乳酸-共-乙醇酸纳米粒负载氟哌啶醇，可得到粒径分布窄且小于 135nm 的纳米粒。这些纳米粒表现出高的刀豆球蛋白 A（STL）结合效率、包封效率和载药量。在 96 小时内，氟哌啶醇在内涵体-溶酶体条件下的体外释放量为加载量的 6-8%，表明药物泄漏最小，有潜力将药物高效递送到靶向脑组织。在侵蚀时释放的氟哌啶醇成功地置换了 [(3)H] N-丙基-降-吗啡，并与牛纹状体多巴胺 D2 受体结合。两种负载氟哌啶醇的纳米粒制剂都能有效地诱导僵住症。与非 STL 功能化颗粒和其他给药途径相比，鼻内给予 STL 功能化纳米粒可使脑组织中氟哌啶醇的浓度增加 1.5-3 倍。这种制剂有望减少治疗精神分裂症所需的抗精神病药物的剂量，以产生治疗效果。
