Fabrication Of Drug Delivery Systems Based On Dextran Microgels And Mesoporous Silica Nanoparticles

One of the future directions of modern pharmacy is improving the performance of drug without changing its structure and ingredient,such as favorable stability,low toxicity and side effects,high drug availability,sustained release,targeting ability.In this study,we have fabricated a kind of microgels that can be used to load drugs and sustainably release it,and a type of mesoporous nanoparticle drug delivery systems that can passively target tumor tissue and release drugs in tumor cel s.Firstly,we used carboxymethyl dextran and amino functionalized zinc oxide quantum dots(ZnO QDs)as the materials to fabricate organic-inorganic hybrid microgels through electrostatic interaction with ZnO QDs as the crosslinker.The microgels can degrade under acidic condition.The drugs were loaded into the microgels through diffusion.We studied the pH depended drug release behaviors in vitro,and found that 70% of drug was released after 60 h at p H 3.0,while 45% of drug was released at p H 7.4,indicating that the dextran microgels are sensitive to pH values and can achieve sustained drug release.Secondly,we fabricated a pH-sensitive mesoporous silica nanoparticle(MSN)drug delivery system.The drug was loaded in the pores of MSNs,and then the MSNs were covered with a kind of cell-penetrating peptide,deca-lysine sequence(K10).Subsequently,citraconic anhydride was used to react with the amine groups on the side chains of K10 to form the acid-labile β-carboxylic amides,transforming the positively charged MSNs to negatively charged ones.Finally,positively charged ZnO QDs were introduced to cap MSNs via electrostatic interaction.The MSN drug delivery system can accumulate in tumor tissue through EPR effects and ZnO QDs nanovalves can be opened in acidic endosomes of cancerous cells,with the following drug release and apoptosis of the tumor cel s.