Abstract
Introduction: 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 into 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.
Keywords: Parkinson's disease, ropinirole, carbopol 934, solid lipid nanoparticles, nanostructured lipid carriers, hydrogel.
Graphical Abstract
[http://dx.doi.org/10.1007/s00702-017-1686-y] [PMID: 28150045]
[http://dx.doi.org/10.1016/j.neuron.2019.03.004] [PMID: 30897356]
[http://dx.doi.org/10.1016/S1474-4422(06)70471-9] [PMID: 16713924]
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[http://dx.doi.org/10.1016/j.lfs.2019.03.057] [PMID: 30980848]
[http://dx.doi.org/10.1586/14737175.4.4.581] [PMID: 15853577]
[PMID: 19557097]
[http://dx.doi.org/10.2165/00003495-200060010-00007] [PMID: 10929932]
[PMID: 19503779]
[http://dx.doi.org/10.1038/nrd1304] [PMID: 15040576]
[http://dx.doi.org/10.1016/j.ejpb.2006.03.009] [PMID: 16797171]
[http://dx.doi.org/10.2174/1567201052772915] [PMID: 16305405]
[http://dx.doi.org/10.1016/j.xphs.2020.01.030] [PMID: 32035925]
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.066] [PMID: 31026490]
[http://dx.doi.org/10.1080/03639045.2020.1788069] [PMID: 32598194]
[http://dx.doi.org/10.3390/nano9010033] [PMID: 30591688]
[http://dx.doi.org/10.1016/j.chemphyslip.2020.104981] [PMID: 33031802]
[http://dx.doi.org/10.1124/jpet.119.256446] [PMID: 30872389]
[http://dx.doi.org/10.1016/j.chemphyslip.2020.104953] [PMID: 32814084]
[http://dx.doi.org/10.1016/j.ejpb.2016.10.022] [PMID: 27810472]
[http://dx.doi.org/10.3109/10717544.2014.914986] [PMID: 24865287]
[http://dx.doi.org/10.1080/03639045.2018.1445264] [PMID: 29493289]
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720]
[http://dx.doi.org/10.1016/S0939-6411(03)00067-5] [PMID: 12957632]
[http://dx.doi.org/10.1186/1476-511X-8-6] [PMID: 19243632]
[http://dx.doi.org/10.3390/pharmaceutics12050448]
[http://dx.doi.org/10.1016/j.ijpharm.2015.06.035] [PMID: 26149934]
[http://dx.doi.org/10.1080/21691401.2018.1465068] [PMID: 29688077]
[http://dx.doi.org/10.3109/03639045.2015.1024685] [PMID: 25830370]
[http://dx.doi.org/10.1080/03639045.2017.1304957] [PMID: 28274147]
[http://dx.doi.org/10.1055/s-0042-119947] [PMID: 27992936]
[http://dx.doi.org/10.1080/03639045.2017.1304955] [PMID: 28271908]
[http://dx.doi.org/10.3109/10837450.2012.685655] [PMID: 22612232]
[http://dx.doi.org/10.1007/s12272-011-1014-2] [PMID: 22076770]
[http://dx.doi.org/10.1055/s-0043-102952] [PMID: 28449156]
[http://dx.doi.org/10.1007/s12247-018-9335-z]
[http://dx.doi.org/10.1208/s12249-016-0488-0] [PMID: 26857516]
[http://dx.doi.org/10.1007/s13233-012-0107-1]
[http://dx.doi.org/10.1208/s12249-020-01787-w] [PMID: 32885357]
[http://dx.doi.org/10.2174/2211738508666200517121637]
[http://dx.doi.org/10.1080/03639045.2017.1402918] [PMID: 29124986]
[http://dx.doi.org/10.1016/j.ijpharm.2008.01.045] [PMID: 18343059]
[http://dx.doi.org/10.1007/s13346-020-00871-9]
[http://dx.doi.org/10.1016/j.foodchem.2017.10.010] [PMID: 29120809]
[http://dx.doi.org/10.2174/2211738508666200225113359] [PMID: 32096755]
[http://dx.doi.org/10.3390/pharmaceutics12060572] [PMID: 32575524]
[http://dx.doi.org/10.1016/S0378-5173(98)00092-1]
[http://dx.doi.org/10.3390/ph11040118] [PMID: 30388738]
[http://dx.doi.org/10.37285/ijpsn.2015.8.1.11]
[http://dx.doi.org/10.1016/j.addr.2012.09.021] [PMID: 11311991]
[http://dx.doi.org/10.1007/s40005-016-0232-5]
[http://dx.doi.org/10.4172/jbb.1000254]
[http://dx.doi.org/10.1055/s-0043-119072] [PMID: 28950389]
[http://dx.doi.org/10.1166/asem.2015.1710]
[http://dx.doi.org/10.37285/ijpsn.2016.9.6.2]
[http://dx.doi.org/10.1186/s43094-020-00051-z]
[http://dx.doi.org/10.3109/21691401.2016.1167703] [PMID: 27068140]