Liposomal co-delivery of coenzyme Q10 and vitamin D3 enhances brain deposition and neuroprotection in a rat model of Parkinson's disease.

CONTEXT: Coenzyme Q10 (CoQ10) and vitamin D3 possess established neuroprotective properties; however, their clinical translation in Parkinson's disease (PD) is limited by suboptimal brain penetration.

AIM: This study aimed to develop a liposomal co-encapsulation system of CoQ10 and vitamin D3 and to evaluate its efficacy against free drugs and standard L-DOPA therapy in a PD rat model.

METHODS

Liposomal formulations were prepared by thin-film hydration and characterised for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and in vitro release. Biodistribution of CoQ10 and vitamin D3 was evaluated in rats following intraperitoneal administration. Neurobehavioral, biochemical, inflammatory, and histopathological assessments were conducted in a rotenone-induced rat model of PD.

RESULTS

The optimised formulation exhibited a particle size of 194.1 ± 6.2 nm, PDI of 0.26 ± 0.02, zeta potential of -32.8 ± 2.6 mV, and entrapment efficiencies of 68.4 ± 4.1% (CoQ10) and 77.9 ± 3.4% (vitamin D3), with sustained drug release over 72 h. Biodistribution studies demonstrated significantly enhanced brain uptake, with CoQ10 and vitamin D3 concentrations reaching 8.4 and 0.66 µg/g at 10 h, representing approximately 11-fold and 9-fold increases, respectively, compared with free drug solutions. In the PD model, liposomal treatment improved motor performance and restored catalase, glutathione, dopamine, and BDNF levels, while reducing TNF-α and IL-6 compared with the rotenone group (p < 0.0001). Histopathological analysis confirmed reduced striatal degeneration and preservation of hippocampal architecture.

CONCLUSIONS

Liposomal co-delivery of CoQ10 and vitamin D3 significantly enhances brain delivery and neuroprotection, representing a promising therapeutic strategy for PD.