Research On Nano Drug Delivery Systems From Poly(Lactide/Glycolide) Block Copolymers

The population of hypertension in China has reached 300 million,and one person dies of cardiovascular and cerebrovascular diseases every 15 seconds,and more than 50%of strokes and myocardial infarctions are related to increased blood pressure.Therefore,people need strong blood pressure reduction so that patients can minimize the risk of cardiovascular events and death is the fundamental reason for achieving blood pressure standards.The existing treatment of hypertension is mainly through oral medication,but there are disadvantages such as the need to take the medication daily and the patient’s non-compliance.The nano-drug delivery system has the advantages of long circulation,slow release,and realization of hydrophobic drug encapsulation,which is of great significance for the treatment of hypertension.Due to the advantages of biocompatibility,biodegradability,and performance controllability,synthetic polymer biomaterials are increasingly used in the field of medicine.Among them,poly(lactide/glycolide)(PLGA)copolymer,because its degradation rate can be adjusted by the ratio of two components,has become a research hotspot of biodegradable materials.In the field of drug delivery,hydrophilic polyethylene glycol(PEG)is introduced to change the chain structure of block copolymers to meet the requirements of the biomedical field.In this project,a poly(lactide/glycolide)-polyethylene glycol(PLGA-PEG)nano-drug delivery system loaded with valsartan was constructed and related performance studies were carried out.In order to build a new nano-hypertension delivery system,this topic uses monomethoxy PEG as a macromolecular initiator,through the ring-opening polymerization reaction of D,L-lactide and glycolide,synthesized block copolymers of PLGA-PEG with different compositions.The obtained copolymer was characterized by nuclear magnetic resonance,gel permeation chromatography and critical micelle concentration analysis.The self-assembly of the copolymer produces aggregates of different structures,including spherical micelles and mixtures of spherical and wormlike micelles.It is also found that the self-assembly structure depends on the ratio of hydrophilic/hydrophobic blocks and the molecular weight of the copolymer.To evaluate the compatibility of hypertension drugs and nano-drug delivery system,the PLGA-PEG drug delivery system was constructed using the anti-hypertensive drug valsartan as the drug model.Studies have found that worm-like micelles have higher drug loading.In vitro drug release in p H 7.4 phosphate buffered saline at 37°C,the initial burst release was detected in all cases,and then slowly released for up to 9 days.It was also found that the release rate of the drug in the micelles largely depends on the degradation of the micelles.Copolymers with short PLGA blocks show faster drug release due to faster degradation of the micelles,while worm-like micelles show slower drug release compared to spherical ones.Therefore,PLGA-PEG copolymer micelles with high drug loading,different structures and variable drug release rates have good application prospects for the sustained delivery of valsartan.Learn more about the interaction of valsartan drug molecules with copolymers at the molecular level.Here,this subject uses a series of experimental techniques combined with Atomic Molecular Dynamics(MD)simulation to study this complex problem.The interaction between valsartan and PLGA copolymer was analyzed.The research in this subject provides insights into the spherical micellar drug delivery system,which shows that PLGA-PEG nanoparticles have a limited ability to accumulate hydrophobic drugs due to the fact that the drug molecules are only located at the water-polymer interface.It further validates the advantages of worm-shaped micellar carriers for encapsulating valsartan,and these findings can be used to rationally design and develop drug delivery systems based on amphiphilic copolymers.In addition,PLGA-PEG micelles have nanostructures.As a drug carrier,various aspects of their biocompatibility need to be studied,including MTT analysis,agar diffusion test,hemolysis test,dynamic coagulation time,and in vivo zebrafish embryonic phase.Capacitive.The comprehensive results show that PLGA-PEG micelles have good cell compatibility and blood compatibility in vitro.Moreover,micelles showed no toxic effects during the entire zebrafish embryonic developmental stage.In summary,this project has prepared a series of PLGA-PEG micelles with excellent biocompatibility through self-assembly.Using the antihypertensive drug valsartan as a model,a micellar drug delivery system was constructed and explored.The drug-loading performance and drug-release performance,combined with computer simulation technology,the interaction between valsartan and PLGA copolymer was analyzed.Based on the analysis of the properties of valsartan and the feasibility of PLGA-PEG as a nano-drug delivery system in this topic,the PLGA-PEG drug delivery system constructed in this topic has potential application prospects in the sustainedrelease delivery of antihypertensive drugs.Further clinical trials laid the foundation.