Study On Poly(N-Vinylpyrrolidone)-b-Poly(Hydroxyethyl Methacrylate) Block Copolymers

Amphiphilic block copolymers which respond to pH,enzyme,temperature others have potential applications in the fields of drugs and gene carriers,biomimetic materials,sensors,etc.Poly(N-vinylpyrrolidone)(PNVP)is a polymer with good biocompatibility,physiological inertness,chemical stability and non-toxicity.It has been widely used in medicine,materials,food and cosmetics industries.Poly(hydroxyethyl methacrylate)(PHEMA)is widely used in biomedical equipment and drug delivery systems due to its good biocompatibility,thermal and chemical stability,and adjustable mechanical properties.The copolymer of N-vinylpyrrolidone(NVP)and hydroxyethyl methacrylate(HEMA)can combine the excellent properties of the two,but currently there are few reports on pH and enzyme responsive amphiphilic block copolymers of NVP and HEMA.In this paper,three amphiphilic block copolymers PNVP-Phe-Lys-b-PDHEMAm(m=1-3,represents the gradual increase in molecular weight of PDHEMA)with different chain segment ratios based on hydrophilic linear PNVP and hydrophobic ketal-protected PHEMA linked by a phenylalanyl-lysine dipeptide were synthesized by with different chain segment ratios phenylalanyl-lysine(Phe-Lys)dipeptides were synthesized by combining the reversible addition-fragmentation chain transfer(MADTX/RAFT)radical polymerization and atom transfer radical polymerization(ATRP).The same method was used to prepare three amphiphilic block copolymers PNVP-b-PDHEMAm(m=1-3,representing the molecular weight of PDHEMA gradually increase)of N-vinylpyrrolidone and hydroxyethyl methacrylate with different segment ratios.The copolymers were characterized by hydrogen nuclear magnetic resonance(1H NMR)spectra and gel permeation chromatography(GPC).The self-assembly behavior and stimulus response performance of the copolymers in aqueous solution were investigated by fluorescence spectroscopy,transmission electron microscope(TEM)and particle size analyzer.The results show that both PNVP-Phe-Lys-b-PDHEMAm and PNVP-b-PDHEMAm can self-assemble to form vesicle aggregates in aqueous solutions.Their critical micelle concentration(CMC)decreases with the increase of the hydrophobic chain length,and the vesicle size increases with the increase of the hydrophobic chain length.The vesicles from PNVP-b-PDHEMA₃ and PNVP-Phe-Lys-b-PDHEMA₃ were used to encapsulate the anticancer drug paclitaxel(PTX),and the drug release performance of these two drug-loaded vesicles was studied and compared.The results showed that the maximum drug loading and encapsulation efficiency of PNVP-Phe-Lys-b-PDHEMA₃ were greater than those of PNVP-b-PDHEMA₃.Under weakly acidic(pH 5.0)conditions,both copolymer drug-loaded vesicles can disassemble to release the contained PTX,which show pH responsiveness.PDHEMA-Phe-Lys-b-PDHEMA₃ drug-loaded vesicles can also release PTX under the action of trypsin;and the drug release rate is the fastest under the action of weak acidity(pH 5.0)and enzymes,indicating that PDHEMA-Phe-Lys-b-PDHEMA₃ has pH and enzyme dual responsiveness.