Novel Nose-to-brain delivery of carbenoxolone via mucoadhesive solid lipid nanoparticles for Parkinson's symptoms management: In vitro and in vivo evaluation in a rotenone-induced rat model.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by motor and non-motor symptoms, with limited effective treatment options. This study proposes a novel approach utilizing intranasal delivery of carbenoxolone (CBX) via chitosan-coated solid lipid nanoparticles (CS-coated SLNs) to manage PD symptoms by enhancing CBX delivery and brain targeting. Formulated CS-coated SLNs exhibited favorable quality attributes including particle size (164 ± 0.12 nm), surface charge (18 ± 0.89 mV), high entrapment efficiency (97.98 ± 0.98 %), and sustained drug release profile. In vivo evaluations in a rotenone-induced rat model of PD involved intranasal administration of CBX suspension and CBX-loaded CS-coated SLN (equivalent to 20 mg/kg/day) over four weeks. The CBX nano-formulation group showed significant improvements in motor function, coordination, and balance, as well as modulation of neurotransmitter levels, with increased dopamine and decreased α-synuclein levels compared to the control group. Moreover, the CBX nano-formulation exhibited superior efficacy in reducing neuroinflammation, oxidative stress, and apoptosis markers. Histological examination revealed restored neuronal architecture, suggesting potential neuroprotective effects. In conclusion, mucoadhesive chitosan-coated SLNs offer a promising nasal delivery system overcoming brain drug delivery obstacles facing CBX therapy in PD, paving the way to the development of novel treatments and improved quality of life for PD patients.