Stearyl amine coated liposome of rotigotine alleviates cognitive deficit in Parkinson's disease induced mice model: modulation of oxidative stress, and motor coordination.

Abstract

Objective: The study was conducted to evaluate the brain targeted delivery of cationic liposomes of rotigotine via nasal route, addressing the limitations in brain penetration for Parkinson's disease intervention.

Methods: Cationic liposomes were fabricated and optimized using a Box-Behnken design to improve the excipient composition for effective intranasal delivery. The optimized liposome, LR12, was surface modified with stearylamine at three concentrations to confer a cationic charge. The final formulation, RTG-LP3, was evaluated for physicochemical parameters, including size, entrapment efficiency, and zeta potential. A morphological study was performed within the 100-200 nm size range. The cytotoxicity of RTG-LP3 was determined in SH-SY5Y cell lines, whereas pharmacodynamic studies were evaluated in C57BL/6 mice following nasal administration.

Results: The formulation RTG-LP3 exhibited a minimal vesicle size of 162 ± 2.94 nm, a high entrapment efficiency of 86.53 ± 0.33%, and a positive zeta potential of +19.8 ± 2.45 mV. Morphological investigation indicated spherical shape of liposomes in the size range of 100-200 nm. Cytotoxicity study showed fivefold safety margin for RTG-LP3 when compared with rotigotine. Pharmacodynamic assessments in PD-induced C57BL6 mice showed increased motor coordination and antioxidant benefits following nasal treatment. Histological study of brain regions treated with RTG-LP3 demonstrated improved neuronal architecture, indicating reduced neurodegeneration and improved disease condition.

Conclusion: The cationic liposome RTG-LP3 demonstrated effective delivery of liposomes with superior therapeutic effects in treating PD via nasal route. These findings highlight the potential of cationic liposomes as a viable method for improving brain penetration and neuroprotection in PD therapy.