Brain-Targeted Delivery of Ropinirole byMucoadhesive Intranasal NanostructuredLipid Carriers for Parkinson’sDisease Management

Abstract

Background: The therapeutic efficiency of orally delivered ropinirole (RP) is reduced due to extensive metabolic
degradation during first-pass metabolism, resulting in moderate bioavailability and increased dosing frequency. To
address these limitations, the present study aimed to prepare and evaluate mucoadhesive nanostructured lipid carriers
(NLCs) of RP for intranasal (i.n.) administration to facilitate brain targeting. Materials and Methods: RP-NLCs
were developed using the solvent diffusion method and optimized through a Box-Behnken design. Glyceryl
monostearate and oleic acid were employed as lipid matrices, while Tween 20 and Pluronic F-68 functioned
as surfactant and co-surfactant. Results and Discussion: The optimized formulation (RF13) exhibited a drug
content of 98.12 ± 2.53% and entrapment efficiency of 95.18 ± 2.69%. The nanoparticles showed a mean particle
size of 150.6 ± 2.13 nm, polydispersity index of 0.377 ± 0.14, and zeta potential of −33.8 ± 2.54 mV, indicating
stable and uniform dispersion. In vitro studies demonstrated sustained drug release of 96.22 ± 3.25% over 4 h,
while ex vivo permeation through goat nasal mucosa showed enhanced diffusion of 98.23 ± 2.25%. The addition
of a mucoadhesive agent significantly improved detachment stress (6131.25 ± 1.22 dyne/cm2) compared with
the non-mucoadhesive system (3678.75 ± 3.24 dyne/cm2). In vivo pharmacokinetic studies confirmed higher
brain uptake with a Cmax of 8.527 ± 0.54 μg/mL and plasma concentration of 1.876 ± 0.56 μg/mL at 1.5 h (Tmax),
supporting direct nose-to-brain transport. Conclusion: Findings of current research suggest that i.n. mucoadhesive
RP-NLCs provide an effective delivery system for enhanced brain targeting, offering the potential to improve PD
management while minimizing systemic adverse effects.