Preparation And Properties Of Folate Modified Copolymer Composite Micelles

Compared with traditional single micelles,compound micelles have higher utilization rate of drug contained in them,and the release of drugs is easier to control In this paper,four different amphiphilic block copolymers FA-PEG-b-PCL,PNVCL-b-PCL,FA-PEG-b-PLA and PNVCL-b-PLA were designed and prepared.Among them,the end groups of polyethylene glycol(PEG)on FA-PEG-b-PCL and FA-PEG-b-PLA are connected with a folic acid group that can achieve the function of active targeted drug delivery.The block junctions of the four block copolymers are acid-sensitive imine bonds.Based on these block copolymers,composite micelles were prepared and characterized by self-assembly.The following is the specific research content:1.First,the telechelic polymer polyethylene glycol(H2N-PEG-OH)was used to acylate with folic acid to synthesize the folate-modified telechelic polymer polyethylene glycol(FA-PEG-OH).Subsequently,FA-PEG-OH and p-hydroxybenzoic acid were esterified to modify the terminal hydroxyl group of FA-PEG-OH into an aldehyde group(FA-PEG-CHO);using mercaptoethanol(HSCH2CH2OH)as a chain transfer agent,even Azobisisobutyronitrile(AIBN)is used as an initiator to ring-open and polymerize N-vinyl caprolactam(NVCL)to obtain hydroxyl-terminated poly-N-vinyl caprolactam(PNVCL-OH).Immediately followed by esterification of p-hydroxybenzoic acid with PNVCL-OH to synthesize aldehyde-terminated poly-N-vinyl caprolactam(PNVCL-CHO);using stannous octoate and N-(tert-butoxycarbonyl)ethanolamine to initiate D L-lactide and ?-caprolactone undergo ring-opening polymerization,and after a series of operations such as deprotection group,the amino-terminated polylactic acid(NH2-PLA)and the amino-terminated polycaprolactone(PCL-NH2).The Schiff bases of amino groups and aldehyde groups are used to prepare block copolymers FA-PEG-b-PCL,FA-PEG-b-PLA,PNVCL-b-PCL,and PNVCL-b-PLA2.Let the block copolymers FA-PEG-b-PCL and PNVCL-b-PCL self-assemble in water to form composite micelles with hydrophilic end PEG and PNVCL as the composite shell,and hydrophobic end PCL as the core;The FA-PEG-b-PLA and PNVCL-b-PLA self-assembled in water to form a composite micelle with the hydrophilic end PEG and PNVCL as the composite shell and the hydrophobic end PLA as the core.The morphology of the micelles obtained by transmission electron microscopy and nanometer particle size analyzer is basically spherical.It can be known from the in vitro release experiment that the compound micelles have a drug release rate lower than 25? at 37? at the same pH;at the same temperature,the release rate of compound micelles at pH=5.0 is greater than pH=7.4.MTT experiments showed that the toxicity of the two compound micelles to MCF-7 cells is very low.In vitro cell endocytosis experiments of compound micelles show that micelles can be endocytosed by MCF-7 cells...