Fabrication And Properties Of Thermos/pH Responsive Particles By Electrospray

Dual-responsive drug delivery system is a research hotspot in recent years,which can achieve targeted drug delivery and intelligent drug delivery [1-4].Gastric cancer is the fourth most common malignant tumor and the second major cause of cancer-related mortality [5,6].Oral gastric cancer drugs can directly act on the stomach,but oral gastric cancer drugs still have many problems to be tackled,such as excessive metabolism,gastric acid erosion and so on [7-9].In this paper,p H/temperatureresponsive and DOX and Apatinib loaded core-shell particles(dual-responsive and dual-drug loaded particles,DD particles)were prepared as a new attempt of oral gastric cancer drugs.In the first part of the experiment,the dual-responsive particles were designed and studied.Firstly,4-para-aminofluorobenzoic acid(4-CBS)was grafted onto chitosan to synthesize 4-CBS-Chitosan with higher adhesion and sensitivity to mucosa,and it was used as a p H-sensitive carrier.Poly-N-isopropylacrylamide(PNIPAM)was used as a temperature-sensitive carrier.Particles with three different structures were prepared: PNIPAM as outer layer and 4-CBS-Chitosan as inner layer;PNIPAM and 4-CBS-Chitosan mixture as outer layer and methanol solution as inner layer;PNIPAM as outer layer,4-CBS-Chitosan as middle layer and methanol solution as inner layer.Electrostatic spray method was used to fabricate particles in one step.Then,the effects of polymer concentration and injection voltage on the morphology and diameter of the three particles were explored and compared;the three particles were characterized by scanning electron microscopy(SEM)and transmission electron microscopy(TEM);and the collection efficiency of the three particles was tested and compared.In the second part of the experiment,on the basis of the first part of the experiment,we selected one of the particles with better morphology and performance: DD particles with PNIPAM as the outer layer and 4-CBS-Chitosan as the inner.Apatinib and DOX were loaded in their outer and inner layers respectively,and we studied them more deeply.The effects of polymer concentration ratio on the thickness and total diameter of the inner and outer layers of the polymer were discussed.The polymer was characterized by scanning electron microscopy(SEM),transmission electron microscopy(TEM)and Fourier transform infrared spectroscopy(FTIR).The drug release curves,p H and temperature sensitive characteristics of different diameter particles were studied.The drug release principle and degradation process were explored.In vivo experiments were carried out to study the bio-distribution of DD particles.This experiment is based on the first part and in the second part,the best particle prepared in the first part is selected as the carrier and loaded with two drugs.DD particles with smooth surface,narrow particle size distribution,good drug sustained-release characteristics,excellent p H and temperature sensitivity is prepared.In vivo studies show that this particle can adhere to gastric mucosa for a longer time than bare drug.Drugs accumulate less in other non-targeting organs,resulting in fewer side effects.The DD particles prepared in this experiment have great potential in the study of oral drugs for gastric cancer,and the dual-sensitive particles can be loaded into different kinds and quantities of drugs in the future,which has excellent application prospects in the field of drug delivery.