Rasagiline-encapsulated chitosan-coated PLGA nanoparticles targeted to the brain in the treatment of parkinson's disease

ABSTRACT

The aim of this study was to investigate the brain targeting potential of rasagiline-encapsulated chitosan-coated PLGA nanoparticles (RSG-CS-PLGA-NPs) delivered intranasally into the brain. Chitosan-coated PLGA nanoparticles (RSG-CS-PLGA-NPs) were developed through double emulsification-solvent evaporation technique. RSG-CS-PLGA-NPs were characterized for particle size, zeta potential, size distribution, encapsulation efficiency, and in vitro drug release. The mean particle size, polydispersity index, and encapsulation efficiency were found to be 122.38 ± 3.64, 0.212 ± 0.009, and 75.83 ± 3.76, respectively. High-performance liquid chromatography–mass spectroscopy and mass spectroscopy study showed a significantly high mucoadhesive potential of RSG-CS-PLGA-NPs and least for conventional and homogenized nanoformulation. Pharmacokinetic results of RSG-CS-PLGA-NPs in Wistar rat brain and plasma showed a significantly high (**p < 0.005) AUC_0-24 and amplified C_max over intravenous treatment group. Finally, the investigation demonstrated that intranasal delivery of mucoadhesive nanocarrier showed significant enhancement of bioavailability in brain, after administration of the RSG-CS-PLGA-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson’s disease therapy and related brain disorders.

GRAPHICAL ABSTRACT

KEYWORDS:

• Brain pharmacokinetics
• CS-PLGA nanoparticles
• LC-MS/MS method validation
• Parkinson’s disease
• rasagiline

List of Abbreviations:

• AUC, area under curve
• C_max, maximum plasma concentration
• CS, chitosan
• ESI, electrospray ionization
• HQC, high-quality control
• K_e, elimination rate constant
• LLE, liquid–liquid extraction
• LOD, lower limit of detection
• LOQ, lower limit of quantification
• LOQ, lower limit of quantitation
• LOQQC, lower limit of quantification for quality control
• LQC, low-quality control
• MQC, medium-quality control
• PD, Parkinson’s disease
• PLGA, poly(lactic-co-glycolic acid)
• PPT, protein precipitation
• PVA, polyvinyl alcohol
• Q-TOF, quadrupole time of flight
• RSG, rasagiline
• SPE, solid-phase extraction
• t_½, half-life
• T_max, time to C_max
• UHPLC-MS/MS, ultrahigh-performance liquid chromatography–mass spectroscopy and mass spectroscopy

Acknowledgments

I (Dr. Niyaz Ahmad) am grateful to Dr. Arshad Hussain Khuroo, Ranbaxy Research Laborarories, Gurgaon, India and Professor (Dr.) Farhan Jalees Ahmad for the collaboration research study in between University of Dammam, Dammam, Saudi Arabia and Jamia Hamdard (Hamdard University), New Delhi, India.