The Studies On The Synthesis And Drug Controlled Release Behaviour Of Amphipathic Polycaprolacone-b-Polyethylene Glycol Copolymers

The cancer is the greatest threat to human health.Clinical treatments of cancer have many different disadvantages such as high toxic side effects,high risk or long treatment period.Besides,these therapies are based on effective antieancer drugs and targeted drug deliveries.In order to solve these problems,a large number of researchers have focused on developing novel and efficient anticancer drugs with small side effects and intelligent controllable drug carriers.Because of the complex environment of human body and the burnet axiom,the nanoparticles with small sizes,good biocompatibilities have a wide range of application prospects in the drug transport systems.In this paper,in order to meet these requirements,we prepared the polycaprolactone-block-polyethylene glycol copolymer with the terminal carboxyl group(PCL-PEG-CT,IPP);star polycaprolactone-block-polyethylene glycol copolymer with the terminal carboxyl group(sPCL-PEG-CT,sPP),targeted star polycaprolactone-block-polyethylene glycol-p-aminophenylboronic acid copolymer with the terminal carboxyl group(sPCL-PEG-CT-PBA,sPPP)nanomicelles and CaCO3 and Ca3(PO4)2 doping on the sPPP(sPPP/CaCO3/Ca3(PO4)2)nanomicelles by ring-opening polymerization in the presence of stannous octoate(Sn(Oct)2),tetrabutylammonium chloride(TBAC)and tert-Butyl bromoacetate.In addition,size,Zeta potential,crystallization properties and surface morphology of IPP,sPP,sPPP and sPPP/CaCO3/Ca3(PO4)2 self-assembly copolymer nanomicelles were systematically studied.By using triethylamine-treated doxorubicin hydrochloride(DOX)as a drug model drug,the IPP/DOX,sPP/DOX,sPPP/DOX and sPPP/CaCO3/Ca3(PO4)2/DOX drug loaded nanomicelles were obtained by solution blending under dark conditions in different pH environment used for intracellular drug release ability,cytotoxicity and uptake.The results indicated that the IPP,sPP,sPPP and sPPP/CaCO3/Ca3(PO4)2 nanomicelles have appropriate size and great pH sensitivity performance,which have different drug release ability in different pH environment.The DOX loading capacity of IPP2 was 8.14%and its cumulative release of dox at ph 5.0 was 97.13%at 168 h.it exhibited good biocompatibility and low cytotoxicity in cell experiments and could be absorbed by Hela cells and A549 cells quickly and exhibited better therapeutic effect.Moreover,The DOX loading capacity of sPP was highest in these nanomicelles,reaching 9.28%.Cumulative release of dox loaded sPP at pH 5.0 was 89.99%after released 168 h and it exhibited better biocompatibility and lower cytotoxicity than IPP2.The DOX loading capacity of targeted sPPP was 9.13%and its cumulative release of dox at ph 5.0 was 90.06%at 168 h.Cell experiments confirmed that the presence of PBA cannot increase the cytotoxicity and it could increase the release of DOX in A549 cell.The DOX loading capacity of sPPP/CaCO3/Ca3(PO4)2 nanomicelles was 8.71%and its cumulative release of dox at ph 5.0 was 95.66%at 168 h.Cell experiments confirmed that the presence of CaCO3 and Ca3(PO4)2 had no effect on cytotoxicity and could increase the cell uptake for drug loaded nanomicelles.