Chitosan-centered nanosystems as sustained therapeutics for allergic rhinitis intervention: Inhibition of histamine-induced cascades.

Published on Jun 1, 2021in Journal of Controlled Release7.727
· DOI :10.1016/J.JCONREL.2021.05.048
Mengjie Sun6
Estimated H-index: 6
(Ocean University of China),
Di Qin2
Estimated H-index: 2
(Ocean University of China)
+ 2 AuthorsYa Liu21
Estimated H-index: 21
(Ocean University of China)
Allergic rhinitis (AR), histamine-mediated upper airway inflammatory disorder, is characterized by sneezing, itching, airway hyperreactivity, etc. Though it is clinically well-managed by non-invasive inhaled antihistamines, for example, ketotifen (KT, histamine release inhibitor) and cetirizine (CTZ, histamine receptor antagonist), inherent defects of short mucosal in situ retention, frequent administration resulting in irritation to mucosa, and lack of target-specific sequential release of dual drug systems which have been proven to be more effective are inevitable, urging for alternative therapeutic strategies. Recent advances in nanotechnology may be pivotal to generating muco-adhesive nanosystems, which is desirable to prolong local retention, reduce dosing frequency and relieve mucosal irritation. In this regard, KT incorporated and CTZ decorated hydroxybutyl chitosan nanoparticles (K ⊂ CH NPs) were fabricated as nasal adaptive sequential release dual drug system for long-term AR therapy. Nasal adaptive morphology transformation and two-step payload release up to 72 h were achieved in vitro, with ~3-fold higher bio-adhesivity over free drugs appeared. K ⊂ CH NPs achieved longer histamine release inhibition (~24 h) and histamine H1 receptor antagonism (~6 h), compared with free KT&CTZ of ~12 h and ~ 2 h, respectively. The nanosystems provided comparable anti-allergic effect to free antihistamines via successive intranasal dropping in AR rat, while encouragingly, significantly (P < 0.05) better therapeutic efficacy at reduced treatment frequency (every 4 days) and dose (half-dose). Therefore, the outcomes establish K ⊂ CH NPs as effective low-dose and long-interval administered nanosystems to ameliorate histamine-mediated AR inflammation, which could in principal find extensive utilizations in respiratory allergy intervention.
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