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 r...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.展开更多
基金supported by the National Natural Science Foundation of China(No.81872826)the Science and Technology Commission of Shanghai Municipality(No.18ZR1404100)the Shanghai Pujiang Program(No.18PJD001).
文摘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.
