Facile nose-to-brain delivery of rotigotine-loaded polymer micelles thermosensitive hydrogels: In vitro characterization and in vivo behavior study

摘要

A rotigotine (ROT)-loaded polymer micelles thermosensitive gel (ROT-PM-TSG) delivery system was engineered to enhance the solubility of the drug, prolong the residence time, and increase the concentration of the drug in the brain tissue. First, ROT-loaded polymer micelles (ROT-PM) were tailored and optimized. The average particle size, encapsulation efficiency, and drug loading of the ROT-PM were (88.62 +/- 1.47) nm, (93.5 +/- 0.79) %, and (19.9 +/- 0.60) %. The optimal ROT-PM-TSG formulation contained 22% P407 and 2% P188 with a gelation temperature of about 32.3 degrees C and a pH of 5.186. In vivo, the MRT of ROT-PM and ROT-PM-TSG nasal administration was 1.43 and 1.79 times extended than that of the intravenous. In comparison with the intravenous group, the distribution of ROT in olfactory bulb, cerebrum, cerebellum and striatum was 276.6%, 170.5%, 166.5% and 184.4%, respectively. In conclusion, the ROT-PM-TSG system has proven to be a potential application prospect as a ROT nose-to-brain delivery system.