期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 9, 页码 3380-3388出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00402
关键词
brain targeting; intranasal administration; dendrimers; nanotechnology; haloperidol; drug delivery
资金
- Natural Science and Engineering Research Council of Canada [1044]
- Ontario Mental Health Foundation, Canada
- Canadian Institutes of Health Research, Canada
Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.
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