Drug-loaded Polymer Nanospheres Prepared By Phase Separation Method And Their Applications

In last few decades,there has been a considerable research interest in the area of polymer nanospheres that attributed to their widespread applications including drug delivery,gene therapy,immunology analysis,separation and purification of biological molecules.In this paper,aiming the application defects of some drugs(such as resveratrol,aspirin,and heparin),several different types of drug polymer nanospheres were prepared by our research group with the help of the concept of nano-drug delivery and phase separation technique.Moreover,their properties and bio-applications were investigated.The details were presented as follows:(1)Resveratrol(Res)has been speculated to be responsible for the decreased risk of coronary heart disease,cancer,etc.How to improve its solubility in water becomes a key issue.In this paper,a simple method of incorporation of water-insoluble Res into nanoscale poly(lactic-co-glycolic acid)matrix was suggested.The novel particles,resveratrol-poly(lactic-co-glycolic acid)nanospheres(PLGA-Res MSs)were characterized by fourier transform infrared spectroscopy(FTIR),Nano ZS90 Zetasizer,and transmission electron microscopy(TEM).The loading and release characteristics of drug and the bio-properties of the PLGA-Res MSs were also investigated.Results showed that PLGA-Res MSs were blood compatible with low level of cytotoxicity.The platelet activation data of PLGA-Res MSs indicated that they can inhibition of platelet activation.Results also indicated that the PLGA-Res MSs have the potential to be used in nanomedicine due to their good bio-properties.(2)Aspirin is a small molecule drug which can anti-inflammatory,antipyretic analgesic and anti-platelet aggregation.In order to prolong efficacy of aspirin,people often use a polymer which contain hydroxyl group combine with it.Here,we referd to previous research,and synthesized a kind of aspirin derivatives-polyvinyl alcohol(PVA-ASBA).Then,based on phase separation technique,we prepared PVA-ASBA-poly(lactic-co-glycolic acid)nanospheres(PLGA-PVA-ASBA MSs),and studied particle size,the release of the drug,the blood compatibility and cytotoxicity.It was worth mentioning that,under different pH conditions in PLGA-PVA-ASBA MSs drug release studies,we found that aspirin from PVA-ASBA release fastly by hydrolysis at strong acid or alkali.It provided a potential application in the field of biomedical,especially drug delivery.(3)Heparin is commonly used in clinic,which has a strong anticoagulant effect for prevention and treatment of thromboembolic diseases.However,it also bring spontaneous bleeding and other side effects.In this work,a novel kind of heparin functionalized polyurethane nanospheres(PU-Hep MSs)were synthesized by a single-step phase separation method.The blood compatibility and anticoagulant effect of the PU-Hep MSs were investigated using coagulation tests,hemolysis assay,complement and platelet activation detection,cytotoxicity analysis,and drug loading and release study.The results confirmed that the heparin can substantially enhance the anticoagulant properties of PU MSs,and the PU-Hep MSs have the potential to be used as a mild anticoagulant compared to heparin.Furthermore,we synthesized different sizes of PU MSs and PU-Hep MSs through adjust the volume ratio of the two reaction solvents in the preparation process.With the simplicity of the functionalized method,the excellent hemocompatibility and the slow-release of heparin,the PU-Hep MSs with desirable bioproperties can be readily tailored to cater to various biomedical applications.(4)PU-Hep MSs were used to establish an amperometric glucose biosensor(GOx/(PU-Hep)/GCE)that can be applied in whole blood directly.More details of immobilizing glucose oxidase(GOx)on(PU-Hep)/glass carbon electrode(GCE)and its electrochemical behavior in whole blood were presented.The cyclic voltammetric(CV)results indicated that GOx immobilized on the PU-Hep MSs exhibited direct electron transfer reaction,and the CV displayed a pair of well-defined and nearly symmetric redox peaks with a formal potential of-408 mV.The biosensor had good electrocatalytic activity toward glucose with a low detection limit in whole blood.The glucose biosensor did not respond to ascorbic acid(AA)and uric acid(UA)at their concentration normally encountered in blood.The values of glucose is determined by the proposed biosensor are very close with the data provided by biochemistry analyzer with a homologous serum samples,thereby indicating that we prepared GOx/(PU-Hep)/GCE biosensor has high credibility.The development of materials science will bring a new momentum to electrical analysis.