The use of DA structural analogs is another therapeutic strategy to provide continuous DA receptor stimulation. Most agonists present low bioavailability when they are orally administered as free drugs and they have to be administered daily in several doses, since their effect lasts only a short time. They are thus good candidates for being formulated in DDS. With this aim, Wang et al. [22] developed rotigotine loaded PLGA MP (Ro-MP) for the continuous release of this D1/D2/D3 DA agonist. The pharmacokinetic study revealed high and stable
Tubastatin A and striatal drug levels for up to 14 days, as determined by microdialysis in 6-OHDA-lesioned rats. Ro-MP intramuscularly injected combined with pulsatile l-DOPA treatment induced significantly less dyskinesias in rats than the pulsatile l-DOPA monotherapy, although both treatments exerted a
ecological niche similar therapeutic motor effect. The toxicity of MP loaded with different drug concentrations was further evaluated in a 3-month study in monkeys. The toxicological effects were associated with rotigotine pharmacodynamic properties and with the foreign body reaction against PLGA and carboxymethylcellulose sodium, used as MP vehicle. The authors concluded that, at the end of the study, MP exhibited high safety in the monkey model. Toxicological findings recovered to a normal level except for adrenal gland vacuolar degeneration [23].
