title: Colloidal soft nanocarrier for transdermal delivery of dopamine agonist: ex vivo and in vivo evaluation.
abstract: Ropinirole, an antiparkinsoism dopamine agonist, is used to treat Restless Legs Syndrome. However, orally it undergoes degradation in gastrointestinal tract and extensive first pass metabolism, resulting in its poor and variable bioavailability of the commercially available oral tablets. In the present investigation, soft nanocarriers, viz., microemulsion of ropinirole with the globule size of 160.2 ± 3.87 nm and zeta potential of -4.24 mV was explored for transdermal application. Transdermal drug delivery offers benefits such as sustained therapeutic plasma levels of drugs, avoidance of first pass effect, and improved patient compliance. In comparison to the hydrogel, the developed microemulsion enhanced the drug permeation across the rat skin and porcine ear skin by 3.5 and 2 folds, respectively. Further, the developed microemulsion antagonized the catalepsy in the haloperidol-induced catalepsy rat model by 10 folds as compared to the marketed tablets. Additionally, in rotenone induced Parkinsonism rat model, the microemulsion showed improvement in the motor function by 76% whereas the oral tablet showed only 5% restoration of the normal function. Besides this, the developed formulation successfully restored the catalase and superoxide dismutase levels which were significantly reduced by rotenone administration. Overall, the in vivo studies suggested the potential of the developed transdermal microemulsion of Ropinirole as a viable alternative to marketed formulations.
authors.forename: Pratikkumar
authors.initials: P
authors.lastname: Patel
authors.forename: Anuradha
authors.initials: A
authors.lastname: Pol
authors.forename: Sandeep
authors.initials: S
authors.lastname: More
authors.forename: Dhaval R
authors.initials: DR
authors.lastname: Kalaria
authors.forename: Yogeshvar N
authors.initials: YN
authors.lastname: Kalia
authors.forename: Vandana B
authors.initials: VB
authors.lastname: Patravale
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000737:chemistry; D002375:Catalepsy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003102:Colloids / Q000737:chemistry; D004058:Diffusion; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D006244:Hardness; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000502:physiology*; D013501:Surface-Active Agents / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D003102:Colloids; D018491:Dopamine Agonists; D004655:Emulsions; D007211:Indoles; D053769:Nanocapsules; D013501:Surface-Active Agents; C046649:ropinirole