Lipophilic Drugs Delivered To The Brain Via Dendrimers

One of the tricks for sneaking a neurological drug past the blood-brain barrier is to make the molecule lipophilic. Although a greasy compound might slip into the brain easily, it can be tough to get a therapeutic amount of the drug to dissolve in the blood. Consequently, such drugs often are administered in high doses, which can lead to adverse effects. Researchers led by Abhay S. Chauhan of Concordia University, in Wisconsin, and Ram K. Mishra of McMaster University, in Ontario, now show that using poly(amidoamine) dendrimers as drug delivery agents, they can make the lipophilic psychiatric drug haloperidol 100 times as soluble in aqueous solution as the free compound (Mol. Pharmaceutics 2015, DOI: 10.1021/acs.molpharmaceut.5b00402). This solubility boost, which comes by trapping haloperidol molecules between the branching arms of the dendrimer, allows the researchers to deliver the drug via a nasal spray rather than by injection. They found that the intranasal dendrimer-haloperidol system elicits the same response in rats that intravenous injections do, but at a much lower concentration of the drug.