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

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.