Biocompatible mucoadhesive nanoparticles for brain targeting of ropinirole hydrochloride: Formulations, radiolabeling and biodistribution
Wael M. Darwish, Noha A. Bayoumi, N. H. Ebeid
Abstract
Abstract Two nanoformulations with mucoadhesive properties and brain‐targeting mechanisms were designed to deliver the anti‐Parkinson's drug, ropinirole hydrochloride (RH). In the first formulation, RH and the amphiphilic block copolymer methoxy poly(ethylene glycol)‐ b ‐poly(caprolactone) were assembled in a core–shell morphology followed by coating with a mucoadhesive chitosan outer layer producing a multilayer vehicle (MLV). In the second formulation, RH was encapsulated during the polyelectrolyte complexation of two natural polymers, chitosan and alginate producing RH‐loaded chitosan‐alginate polyelectrolyte (PEC) nanocomplex. Conditions of each formulation were adopted for optimal drug loading. Physico‐chemical characterization of the prepared formulations (particle size, polydispersity index and zeta‐potential) exhibited stable monodispersed nanoparticles. RH was radiolabeled by I‐131 radiotracer in a high‐radiochemical yield. Biodistribution and brain targeting of RH from the prepared formulations were studied after administration of 131 I‐RH‐loaded nanoparticles to albino mice via intranasal and intravenous routs. Elevated brain radioactivity was detected post IN administration of ( 131 I‐RH/PCL‐PEG/CS) nanoparticles and ( 131 I‐RH/CS‐ALG) nanoparticles comparing with the IN administrated RH solutions ( C max = 2.8 ± 0.3, 2 ± 0.3, 0.93 ± 0.03% radioactivity/g, 1 h post administration, respectively). This demonstrated that a relatively high‐brain targeting could be achieved via intranasal route of administration of RH‐loaded nanoparticles. The proposed models are further potential for application to deliver many other brain‐targeting therapeutics.