title: Novel surface modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation.
abstract: Here we report fabrication and evaluation of novel surface modified polymer-lipid hybrid nanoparticles (PLN) as robust carriers for intranasal delivery of ropinirole hydrochloride (ROPI HCl). Sustained release, avoidance of hepatic first pass metabolism, and improved therapeutic efficacy are the major objectives of this experiment. PLN were fabricated by emulsification-solvent diffusion technique and evaluated for physicochemical parameters, in vitro mucoadhesion, in vitro diffusion, ex vivo permeation, mucosal toxicity and stability studies. Box-Behnken experimental design approach has been employed to assess the influence of two independent variables, viz. surfactant (Pluronic F-68) and charge modifier (stearylamine) concentration on particle size, ζ-potential and entrapment efficiency of prepared PLN. Numerical optimization techniques were used for selecting optimized formulation sample, further confirmed by three dimensional response surface plots and regression equations. Results of ANOVA demonstrated the significance of suggested models. DSC and SEM analysis revealed the encapsulation of amorphous form of drug into PLN system, and spherical shape. PLN formulation had shown good retention with no severe signs of damage on integrity of nasal mucosa. Release pattern of drug-loaded sample was best fitted to zero order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were executed to compare therapeutic efficacy of prepared nasal PLN formulation against marketed oral formulation of same drug. In summary, the PLN could be potentially used as safe and stable carrier for intranasal delivery of ROPI HCl, especially in treatment of Parkinson's disease.
authors.affiliation: Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Karwand Naka, Shirpur, Dhule, 425405 Maharashtra, India. chandrakantpardeshi11@gmail.com
authors.forename: Chandrakantsing V
authors.initials: CV
authors.lastname: Pardeshi
authors.forename: Veena S
authors.initials: VS
authors.lastname: Belgamwar
authors.forename: Avinash R
authors.initials: AR
authors.lastname: Tekade
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Surana
mesh_terms: D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000978:Antiparkinson Agents; D004337:Drug Carriers; D007211:Indoles; D008055:Lipids; D011108:Polymers; C046649:ropinirole