Drug Delivery and Translational Research - Featured Article: April 2024
Read the featured article from the April 2024 issue! (this opens in a new tab)
Rotigotine (RTG) is a dopamine agonist that exerts anti-Parkinsonian effects through dopamine receptor agonism to improve motor symptoms and overall performance in Parkinson’s disease (PD) patients. In this study, an in situ liquid crystal gel, rotigotine-gel (RTG-gel), was developed using soya phosphatidyl choline (SPC) and glycerol dioleate (GDO) to provide long-acting slow-release of rotigotine while minimizing side effects. The rheological properties of the RTG-gel precursor solution, prepared with SPC, GDO, and ethanol, indicate a favorable combination of low viscosity and excellent flowability. The gel that produced during water absorption was also highly viscous and structurally stable, which helped maintain the delayed drug release at the injection site. In vitro release of RTG-gel followed Ritger-Peppas. The RTG-gel precursor solution, following subcutaneous injection, exhibited the plasma elimination half-life (t1/2) of 59.28 ± 16.08 h, the time to peak blood concentration (Tmax) of 12.00 ± 10.32 h, and the peak concentration (Cmax) of 29.9 ± 10.10 ng/mL. The blood concentration remained above 0.1 ng/mL for 20 days after administration and was detectable after 31 days of administration, and the bioavailability of RTG reached 72.59%. In vitro solvent exchange tests revealed that the RTG-gel precursor solution underwent rapid exchange upon contact with PBS, and the diffusion of ethanol reached 48.1% within 60 min and 80% within 8 h. Cytotoxicity test showed 89.27 ± 4.32% cell survival after the administration of RTG-gel. The administration site exhibited healing without redness and hemorrhage after 14 days of injection. In addition, inflammatory cells decreased and granulation tissue appeared after 14 days of administration, and there was basically no inflammatory cell infiltration after 35 days of administration. Overall, RTG-gel might be a potential RTG extended-release formulation for treating PD.