Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes(CLNs)for enhanced intranasal siRNA delivery

This research aims to develop a non-invasive strategy for small interfering RNA(siRNA)nasal delivery based on ionic liquids(ILs)and cationic lipid(2,3-dioleoyloxy-propyl)-trimethylammonium-chloride(DOTAP).Other than the classical role of penetration enhancer,ILs also acted as superior solvents to simultaneously load siRNA and DOTAP,forming siRNA-DOTAP-ILs(siRNA-DILs)formulations.During nasal mucosa penetration,DOTAP and ILs components self-assembled into cationic lipid nanocomplexes to load siRNA for enhanced in situ transfection.The siRNA-DILs demonstrated resistance against RNase,significant mucosa penetration,prolonged nasal retention,and satisfying gene-silencing efficacy at lower dosage.Meanwhile,DILs were also able to deliver KCa3.1-targeted siRNA effectively for the treatment of allergic rhinitis in rat model by nasal route.Thus,DILs have great potentials to deliver biological macromolecules across nasal mucosa by in situ dynamic self-assembly.

Discriminating against injectable fat emulsions with similar formulation based on water quenching fluorescent probe

The discrimination against nutritional fat emulsion injections was considered by imaging tools,which aims to elucidate the in vivo behaviors of nanoemulsions.In this study,20%nutritional fat emulsion injections were selected from different company including original and generic products.Meanwhile,a water quenching fluorescent probe(P2)was used to label them by an incubation method.The fluorescent intensity analysis of blood-borne fluorescence reveals rapid clearance of nanoemulsion in all groups,which shows'L'-type blood kinetic profiles.However,these kinetic parameters do not have significant difference.Following intravenous administration,the nanoemulsions in all groups concomitantly accumulated in organs of reticulo-endothelial system(RES),such as liver and spleen,and were cleared from body circulation mostly after 12 h.AUC(0-t)of organs from different groups showed dissimilar results in some organs.These intuitional results are of significance in understa nding the in vivo behaviors of nanoemulsions,which can provide a new way to discriminate against nutritional fat emulsions.

Rod-like mesoporous silica nanoparticles facilitate oral drug delivery via enhanced permeation and retention effect in mucus

The physiochemical characteristics of nanoparticles affect their in vitro and in vivo performance significantly,such as diameter,surface chemistry,and shape.This paper disclosed the effect of enhanced permeation and retention(EPR)in mucus caused by nanoparticle shape on improving oral absorption.The spherical and rod-like mesoporous silica nanoparticles(MSNs)were used to evaluate shape effect of EPR in mucus.Fenofibrate was loaded in MSNs as model drug.The in vitro release of fenofibrate from MSNs was dependent on nanoparticle shapes,but faster than that of raw drug.The drug release slowed down with the increase of aspect ratio due to longer channels in rod-like MSNs with higher aspect ratio.However,in vivo study showed that the oral bioavailability of fenofibrate was the highest after loading in rod-like MSNs with aspect ratio of 5.The in vitro study of mechanisms revealed that superior mucus diffusion ability of rod-like MSNs with aspect ratio of 5 was conductive to higher bioavailability.Meanwhile,more rod-like MSNs with higher aspect ratio were able to diffuse into mucus and reside there compared to spherical and short counterparts,which demonstrated higher aspect ratio was beneficial to EPR effect of nanoparticles in mucus.This study provides significant implication in rational oral drug carrier design.