Preparation And Anticancer Study Of Chitosan Coated Hollow PLGA Microspheres

Cancer has always been a threat to human life.At present,the commonly chemotherapy for cancer has many disadvantages which limit its development,so it is necessary to develop better cancer treatment methods.Drug-loaded microsphere can reduce drug toxicity,thus becoming a key means of cancer treatment.Poly(lactic-coglycolic acid)(PLGA)has good biocompatibility and biodegradability,but its application is hindered by the low drug inclusion rate,high drug burst release rate and lack of identifiable cell sites in the molecular chain of pure PLGA microspheres.Chitosan(CS),as a kind of natural biological macromolecule cationic polymer,has attracted much attention because there exist a large number of active groups on the molecular chain that can be introduced into the recognizable sites of cells,so it can be used to modify polymer microspheres.This paper aims to study the drug loading and drug release performance of CS modified composite drug loading microspheres with special structure,and then explore the difference in anticancer effects caused by different drug loading microspheres in structure.It mainly includes the following contents:(1)The improved emulsifying solvent volatilization method combined with the solution-gel transformation characteristics of chitosan at different p H values,CS was successfully coated on the surface of PLGA microspheres by adjusting the p H values of external water phases during the formation of microspheres,and a rough CS shell was formed on the surface of microspheres.At the same time,ammonium bicarbonate(ABC)was added into the internal aqueous phase to form a hollow structure inside the microspheres.(2)The CS modified microspheres were qualitatively analyzed by infrared and thermal analysis.Morphology analysis results show that CS modified microspheres have a special structure of rough shell and hollow inside,and explore the forming mechanism of microspheres morphology.The influence of morphology on the properties of the microspheres was discussed by measuring the basic properties of the microspheres.The results showed that CS modified microspheres had better drug loading ability and the particle size was increased compared with ordinary PLGA microspheres.In vitro release studies showed that composite microspheres had lower burst release rate,faster drug release rate and higher cumulative release rate.(3)Through the cell toxicity experiment,apoptosis and cell cycle,and immunofluorescence and immune protein experiment confirmed the good biocompatibility of blank composite microspheres and drug-carrier microspheres can achieve long-term anti-cancer effect through sustained drug release,and can induce the apoptosis of cancer cells induced apoptosis characteristic to some extent the effect of the concentration dependence.The rough CS shell hollow PLGA drug-loaded microspheres prepared in this topic have good biocompatibility and biodegradability,and have good drug loading performance and drug release performance.The compound microspheres produced long-lasting anticancer effects by degrading and releasing drugs,which inhibited cell proliferation and increased the sensitivity of cancer cells to anticancer drugs.Therefore,CS modified composite microspheres can be used as a reliable anti-cancer drug delivery system.