Parkinson’s disease (rp) is a progressive neurodegenerative disorder. Ropinirole (RP) is a newer generation dopamine agonist used for the treatment of PD. It is prescribed as oral dosage form. However, limited oral bioavailability and frequent dosing limits the RP usage. The objective of the current investigation was to develop, optimize, evaluate pharmacokinetic (PK) and pharmacodynamic (PCD) activity of RP loaded solid lipid nanoparticles (RP-SLNs) and nanostructured lipid carriers (RP-NLCs) and containing hydrogel (RP-SLN-C and RP-NLC-C) formulations for improved oral and topical delivery. RP loaded lipid nanoparticles were optimized and converted to hydrogel using carbopol 934 as the gelling polymer. PK and PCD studies in haloperidol-induced PD were conducted in male Wistar rats. In vitro and ex vivo permeation studies showed sustained release profile and enhanced permeation compared with control formulations. Differential scanning calorimeter and X-ray diffraction studies revealed amorphous transformation; scanning electron microscope showed the spherical shape of RP in lipid nanoparticles. PK studies showed 2.1 and 2.7-folds enhancement from RP-SLN and RP-NLC from oral administration, 3.0 and 3.3-folds enhancement from RP-SLN-C and RP-NLC-C topical administration, compared with control formulations, respectively. RP-SLN-C and RP-NLC-C showed 1.4 and 1.2-folds topical bioavailability enhancement compared with RP-SLN and RP-NLC oral administration, respectively. PCD studies showed enhanced dopamine, glutathione, catalase levels and reduced lipid peroxidation levels, compared with the haloperidol-induced PD model. Overall, the results demonstrated that lipid nanoparticles and corresponding hydrogel formulations can be considered as an alternative delivery approach for the improved oral and topical delivery of RP for the effective treatment of PD.

Purpose: Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration. Aim: The objective of the current research was to develop RP loaded solid lipid nanoparticles (RP-SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that could enhance RP therapeutic outcomes during PD treatment. Methods: RP nanoparticles were prepared by homogenization followed by probe sonication and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), % assay, % entrapment efficiency, and in vitro release studies. Optimized formulations were converted to hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures. Results: The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h. Optimized SLN, NLC, and nanocarrier loaded hydrogel formulations were stable over three months at 4ºC and 25ºC storage conditions. Conclusion: Overall, the results demonstrated that lipid nanocarriers and their corresponding hydrogel formulations can be considered as a topical drug delivery vehicle for RP during the treatment of PD.