Preparation And Properties Of Nanomicelles Modified By In Situ Free Radical Polymerization

The research of Nano Drug Delivery Systems(NDDSs)is one of the most important topics in the 21 st century.In recent years,researchers have developed a variety of nano-drug delivery systems,among which polymer nano-micelles have many advantages,such as easy surface modification,reducing drug toxicity and side effects,delivering small and large molecular drugs,and achieving sustained and controlled drug release.However,when the polymer nano-micelles are injected into the organism by intravenous injection,they will be diluted by plasma,exposed to salt solution environment and interact with plasma proteins,which will lead to the dissociation of polymer nano-micelles before they reach the lesion site,and then lead to drug leakage.In order to improve the stability,researchers have taken various modification methods to modify the polymer nano-micelles.The traditional modification strategy is to design the micelle-forming polymer molecules to achieve covalent or non-covalent interactions between the molecules in the polymer micelles and enhance the stability of the polymer micelles.However,these strategies require complex molecular design in the early stage,which often changes the chemical properties and hydrophilicity of the micelle surface and reduces the blood circulation ability of the micelle.Therefore,it is of great significance to study how to obtain highly stable polymer nanomicelles by a simple and efficient method.In this paper,a variety of drug-loaded polymer nanomicelles were prepared by nano-precipitation method,and the monomers were adsorbed and enriched on the surface of polymer micelles due to the electrostatic interaction and hydrogen bonding interaction between polymer micelles and monomers,and then the polymer nanomicelles were modified in situ by initiating aqueous radical polymerization.A layer of cross-linked reticular polymer shell is formed on the surface of the polymer nano-micelle.Compared with the traditional method,the modification process is simpler and more efficient,and the newly formed polymer shell layer has good hydrophilicity,so that the stability of the polymer nano micelle is greatly enhanced,and a new idea for enhancing the stability modification of the polymer nano micelle is provided.The main contents and conclusions of this paper are as follows:(1)In chapter 2,we prepared polymer nanocarriers by loading paclitaxel(PTX)into Pluronic F127 and methoxy polyethylene glycol-poly(caprolactone)(m PEG5KPCL10K)respectively.We introduced C=C double bonds as active sites for free radical reaction on the surface of the nanocarriers by adding positively charged monomer N-(3-aminopropyl)methacrylamide hydrochloride(APM)and neutral monomer acrylamide(AAM)into the nanocarrier solution.Degradable dimethyl glycerol acrylate(GDMA)and non-degradable N,N’-methylenebisacrylamide(BIS)were used as crosslinkers.The reaction was initiated by ammonium persulfate(APS)and N,N,N’,N’-tetramethylethylenediamine(TEMED)to achieve in situ modification of the polymer nanocarriers.The results showed that after crosslinking modification,the particle size of F127/PTX and m PEG5K-PCL10K/PTX increased from around 30 nm to 60-80 nm,and the Zeta potential changed from negative to positive.The nanocarriers exhibited better stability in salt solution dilution and acidic PBS environment,and showed excellent sustained release and p H-responsive characteristics in vitro drug release.In vitro anti-tumor experiments also showed better therapeutic effects.(2)In chapter 3,in order to further study the properties of polymeric nanomicelles modified by aqueous radical polymerization with different therapeutic drugs,we prepared polymeric nanomicelles loaded with ginsenoside Rg3,curcumin and camptothecin by m PEG5K-PCL10 K,and successfully modified them by aqueous radical polymerization.The results showed that the size of the modified nano-micelles increased from 30 nm to 60 nm,and the nano-micelles showed good spherical structure and uniform dispersion under transmission electron microscopy(TEM).The stability of the modified nano-micelles in salt solution dilution and acidic PBS environment was greatly improved,and the anti-tumor activity in vitro was significantly enhanced.This provides a reference for further design of drug-loaded nano-micelles by selecting a variety of polymer materials and a variety of drugs,and provides a new idea for the stability modification of drug-loaded nano-micelles.