Drug Delivery And Its Performance Design Of Smart Nanoparticle For Mucosal Penetrating

Aiming at the two key mass transfer processes of mucosal drug delivery（penetrating mucus and endocytosed by the mucosal epithelial cells）,two smart nanoparticles with muco-inert and rapid mass transfer rate were prepared in this work,by using biodegradable materials mesoporous silica and poly carboxylbetaine methacrylate（p CBMA）.Firstly,the combination of anti-adhesive zwitterionic polymer p CBMA and the high-speed nanomotor driven by near infrared ray（NIR）,was used to prepared the nanoparticles with fast mass transfer rate and effective endocytosis.In detail,the mesoporous silica nanoparticles（MSNs-NH₂）were synthesized by sol-gel method,and then p CBMA was grafted onto its surface to form muco-inert nanoparticles（MSNs-p CBMA）,and finally Au was deposited on the side of the particles to prepare Janus-type nanomotor（JMSNs-p CBMA）.It was found that JMSNs-p CBMA was heated significantly after NIR irradiation.Moreover,p CBMA and Au-modification effectively improved the mucus penetrating efficiency,achieving 52.4%（with NIR）,which was6.7-fold that of MSNs-NH₂（with NIR）.Besides,the velocity of JMSNs-p CBMA with NIR reached 3.5μm/s,equivalent to 29 body length/s.It is notable that all these four nanoparticles showed low cytotoxicity and good biocompatibility,and in vitro cell uptake test proved JMSNs-p CBMA with NIR exhibited the best endocytosis efficiency.Then,in order to enhance the endocytosis,the acid-sensitive dimethylmaleic anhydride（DMMA）was modified on MSNs-p CBMA,and MSNs-p CBMA-DMMA was obtained.It was found that the zeta potential of MSNs-p CBMA-DMMA changed with p H,exhibiting its acid sensitivity.Furthermore,the mucus penetrating efficiency reached 16.3%,which was 1.9-fold that of MSNs-p CBMA,indicating the acid-sensitivity modification greatly increased the penetration.It is worth noting that all these nanoparticles had low cytotoxicity,and comparing with other particles,MSNs-p CBMA-DMMA showed significantly enhanced cell uptake efficiency in vitro.In short,the muco-inert zwitterionic polymer was successfully combined with the fast motion of nanomotor for the mucosal drug delivery,and the effect of acid-sensitivity modification of muco-inert nanoparticles on the mass transfer process and cell uptake was explored.The experimental results will provide new ideas for mucosal drug delivery design and benefit the potential application of nanomotor in mucosal drug delivery.