Preparation And Drug Release Properties Of Multi-responsive Nano-drug Carriers

Traditional cancer treatment methods are inevitably toxic to normal tissues,because they are directly in contact with the body and need repeated application of drugs,which limits the clinical use of existing treatments.In order to reduce the side effects of drugs and the frequency of repeated administration,drug carriers have become a research hotspot.With the deepening of the research on drug carriers,single-response drug carriers can no longer meet the clinical needs.The requirement of drug carriers has been changed from single response to multiple response or even to multi-functional response which integrates diagnosis and treatment.This can significantly improve the precise release of drugs and reduce the number of doses.With the development of nanoparticles,nanoparticles provide tremendous support for disease prevention,diagnosis and treatment.In the field of biomedicine,nanoparticles have unique advantages in drug delivery and image enhancement.Nano-pharmaceuticals improve existing therapies through pharmacokinetics and biological distribution.In order to prepare nanodrug carrier with high drug loading,low toxicity and multiple environmental responses.The following experiments are carried out in this paper:(1)Polylactide macromonomers with double bond functional groups were prepared by ring opening polymerization of lactide with hydroxyethyl methacrylate(HEMA)as initiator and lactide as monomer under the action of stannous octoate as catalyst.Then PLA-g-P(NIAPM-co-AA)/5-FU loaded micelles were prepared by free radical copolymerization of PLA,N-isopropylacrylamide and acrylic acid with AIBN as initiator.Then PLA-g-P(NIAPM-co-AA)/5-FU loaded micelles were prepared by dialysis with 5-FU as analogue drug and N,N'-dimethyl sulfoxide as solvent.TEM,SEM,1H-NMR,FT-IR,CMC and particle size were measured.The results show that the polymer-loaded micelles have obvious core-shell structure,and the particle size range of the micelles is 58±17 nm.The micelles have good pH response and anti-dilution ability.There was no sudden release during drug release.5-FU was released slowly in weak acidic environment.It has good sustained and controlled release effect and can be used for targeted anti-cancer therapy.(2)PLA-g-P(NIAPM-co-AA)/5-FU nanocapsules and PLA-g-P(NIAPM-co-AA)/cabazitaxel nanoscale nanocapsules were prepared by microemulsion polymerization using twelve alkyl sulfate(SDS)as emulsifier,PLA,NIPAM and AA as monomers,two vinyl benzene(DVB)as crosslinking agent,5-fluorouracil(5-FU)and cabazitaxel as mimic drugs.PLA-g-P(NIAPM-co-AA)nanocapsules have good pH and temperature responsiveness.The drug release rate of 5-FU nanocapsules is higher at low temperature and weak alkalinity.The drug release rate of cabazitaxel nanocapsules is higher at high temperature and weak acidity.(3)Fe3O4 magnetic particles were prepared by coprecipitation method.Then N-isopropyl acrylamide was used as thermo sensitive monomer and acrylic acid as pH sensitive monomer.Cabazitaxel match was used as a mimie drug,and P(NIPAM-co-AA)/Fe3O4 magnetic nanocapsules were prepared by emulsion polymerization and nanocapsules loaded with cabazitaxel.TEM results showed that the magnetic nanocapsules had spherical core-shell structure.P(NIPAM-co-AA)/Fe3O4 magnetic nanocapsules loaded with cabazitaxel have good magnetic response performance.The drug release rate in weak acidic environment is significantly higher than that in weak alkaline environment.It shows that cabazitaxel can be transported to the tumor site by external magnetic field,and drug release rapidly in the tumor site can greatly improve the targeted therapeutic effect.