Formulation of intranasal surface engineered nanostructured lipid carriers of rotigotine: Full factorial design optimization, in vitro characterization, and pharmacokinetic evaluation

The objective of the present research was to develop, optimize, and evaluate rotigotine (RT)-loaded chitosan (CH) coated nanostructured lipid carriers (RT-CH-NLCs) for nose-to-brain delivery. The NLCs were prepared by homogenization and sonication technique as well as optimized by using three factors at three-level Box-Behnken design. The prepared NLCs were evaluated for particle size, zeta potential, entrapment efficiency, drug release, and ex vivo permeation. The pharmacokinetic study was conducted on albino Wistar rats to evaluate the bioavailability and neuropharmacokinetic parameters after intranasal administration of the optimized formu-lation (RT-CH-NLCs-OPT). The optimized formulation showed the particle size (170.48 +/- 8.37 nm), PDI (0.19 +/- 0.03), zeta potential (+26.73 mV), and entrapment efficiency (82.37 +/- 2.48 %). In vitro drug release study displayed a sustained drug release pattern from RT-CH-NLCs-OPT (86.73 +/- 8.58 % in 24 h) in comparison to RT-Dis (98.61 +/- 7.24 % in 16 h). The permeability coefficient (PC) was found to be 11.39 +/- 1.08 x 10-4 cm.h-1 and 2.34 folds higher than RT-Dis (4.85 +/- 1.53 x 10-4 cm.h-1). The relative bioavailability of RT from RT-CH-NLCs-OPT was 3.2-fold greater as compared to RT-Dis. The absolute bioavailability of RT after intranasal adminis-tration of RT-CH-NLCs-OPT was 2.1-fold higher than RT-CH-NLCs-OPT administered intravenously. The brain targeting and targeting potential was displayed by DTE (422.03 %) and DTP (76.03 %) after intranasal administration of RT-CH-NLCs-OPT as compared to RT-Dis (DTE 173.91 % and DTP 59.97 %). Furthermore, confocal laser scanning microscopy results confirmed better brain targeting for RT-CH-NLCs-OPT as compared to RT-Dis. From these findings, it could be concluded that RT-CH-NLCs could serve as a promising strategy for targeting RT through the intranasal route.

Automated summary

The objective of this research was to develop, optimize, and evaluate rotigotine-loaded chitosan coated nanostructured lipid carriers for nose-to-brain delivery. The optimized formulation showed small particle size, high encapsulation efficiency, sustained drug release, and improved brain targeting potential. The results suggest that this formulation could be a promising strategy for targeting rotigotine to the brain via intranasal administration.