Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation

Abstract

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing.

PEO-b-PCL/Tween 80/cyclodextrin systems: from bioinspired fabrication to possible nasal administration of ropinirole hydrochloride

“…The findings extracted from the DSC experiments for pure compounds of Tw80, MβCD, and HPβCD, as well as their combinations (Tw80/MβCD 70 : 30 and Tw80/HPβCD 70 : 30), are comprehensively documented in our recent study. 31 Briefly, the thermogram analysis of Tw80 (ESI,† Fig. S1B) showed a broad endothermic peak at 60 °C, which may be coincident with the cloud point of Tw80 at 65 °C.…”