The Preparation Of PEG-PCL-PEI Nanoparticles And Study On The Release Of NBP Drugs

Biodegradable polyesters,such as polycaprolactone(PCL),are not only widely used as human tissue engineering scaffolds(such as tissue repair devices and surgical sutures)due to their excellent biodegradability and biocompatibility,but also used as substrates for drug delivery systems due to their excellent drug permeability.However,since PCL is a hydrophobic polymer with strong crystallization and slow biodegradation rate,it has some limitations to control the degradation rate only by adjusting its molecular weight and its distribution.After the segment of the amphiphilic polyethylene glycol-polycaprolactone block copolymer(PEG-PCL)is modified with various ligands(such as peptides,antibodies,carbohydrates,aptamers and small molecules,etc.),Not only can it improve its original shortcomings,but also hope to enhance the bioavailability of drugs and achieve targeted drug delivery.In this thesis,ring-opening polymerization was first used to synthesize amphiphilic PEG-PCL block copolymer,and then the polyethylene addition(PEI)was grafted by Michael addition reaction to prepare PEG-PCL-PEI nanoparticles.Finally,the in vitro release properties of nanoparticles loaded with3-n-butylphthalide(NBP),which is a kind of medication for acute cerebral infarction will be investigated,The phased research results obtained are as follows:1?Firstly,PEG was synthesized using potassium bis(trimethylsilyl)amide(KHMDS),an organic strong base with a large steric hindrance,as the initiator and ethylene oxide monomer as the raw material.Using the characteristics of PEG macromolecule to initiate the ring-opening polymerization of?-caprolactone,Amphiphilic PEG-PCL block copolymers with different molecular weights were prepared using the monomer addition method and solvent evaporation method(PEG2k-PCL2k?PEG5k-PCL2k and PEG5k-PCL5k).The composition,molecular weight and molecular weight distribution of the PEG-PCL block copolymer and the morphology and particle size of the nanoparticles were analyzed by Fourier-transform infrared(FT-IR)spectroscopy,Gel permeation chromatography(GPC),Hydrogen nuclear magnetic resonance(~1HNMR)dynamic laser scattering(DLS),Scanning electron microscope(SEM)and Zeta potential analyzer.The preparation method can not only synthesize copolymers with different molecular weights and different segment ratios more conveniently,but also have good molecular weights and molecular weight distributions.2?Secondly,polyethylenimine(PEI)was grafted onto the segment of the PEG-PCL block copolymer using Michael addition reaction to prepare the PEG-PCL-PEI block copolymer.Three PEG-PCL-PEI copolymer nanoparticles with different molecular weights were prepared by solvent evaporation method.The results show that the molecular weight and molecular weight distribution of PEG-PCL-PEI block copolymers with the three different molecular weights are close to the theoretical calculation,and the molecular weight distribution is narrow.The particle size of PEG-PCL-PEI polymer nanoparticles is 150?200 nm,and the Polydispersity Index is within0.2,and the Zeta potential is 5?10 m V.In the PEG-PCL block copolymer nanoparticles,the introduction of PEI is expected to shield the excessively high negative charge of PEG-PCL,reduce non-specific binding,reduce toxicity,enhance the water solubility and biocompatibility of the nanoparticles.It is an excellent carrier for sustained drug release.3?Finally,explore the sustained release behavior of PEG-PCL-PEI copolymer nanoparticles loaded with NBP drugs.To study the drug loading(DL)and entrapment efficiency(EE)of three different molecular weight copolymer nanoparticles loaded with NBP,as well as the in vitro sustained release behavior in PBS buffer solution at pH=1.2(simulating human gastric juice environment)and pH=7.4(simulating colonic fluid environment).The results show that when the NBP drug content is 40%,the nanoparticle drug delivery system has the best DL and EE.The comprehensive performance of PEG5k-PCL2k-PEI nanoparticle drug-loading system is superior to the other two systems.Simultaneously,PEG-PCL-PEI nanoparticles loaded with NBP drugs are released more efficiently in human gastric juice environment than in human colon fluid environment(pH=7.4).