Preparation Of PH/Thermo-responsive Polymer ?PCL-PDMAEMA-PPEGMA?₄ And Its In Situ Gel For Anticancer Drug Delivery

Hydrogels have been widely exploited in the prospective applications of drug delivery,owing to good biocompability and unique three-dimentional network structure.Injectable hydrogels are injected into the target site in a liquid form,and form hydrogels in situ when responding to the significant change of temperature.Afterwards the in situ hydrogel release drug continuously in response to a specific stimulus of tumor sites,which is especially suitable for solid tumor treatment.In this study,a kind of biodegradable four-arms star-like block polymer was designed and synthesized.The polymer solution is able to transite to hydrogel spontaneously as temperature increases from 25?to 37?due to inherent temperature response.Moreover,the hydrogel can also respond to the p H value of the tumor site?pH 6.5?,and controlls the release of the antitumor drug doxroubicin?DOX?.The main contents are presented as following:The ring-opening polymerization?ROP?and the atom transfer radical polymerization?ATRP?were applied to prepare the polymers.The four-arms poly caprolactone?PCL?₄ was prepared via the ROP of?-caprolactone.Then?PCL?₄ was polymerized with poly?N,N-dimethylaminoethyl methacrylate??PDMAEMA?and monomethoxy polyethylene glycol methacrylate?PEGMA?step by step using ATRP,and the four-arms star-like amphiphilic block polymers?PCL-b-PDMAEMA-b-PPEGMA?₄ were synthesised successfully.The molecular weight and distribution of the polymer were characterized by gel permeation chromatography?GPC?,the structures of the polymers were characterized by fourier transform nuclear magnetic resonance?¹H-NMR?.In aqueous solution,the polymer could self-assembly into micelles,which consists of a hydrophobic core with PCL,a pH-sensitive layer with PDMAEMA,and a hydrophilic shell with PPEGMA.We investigated the polymeric micellization behavior through the determination of critical micelle concentration?CMC?by using fluorescence spectroscopy.The particle size of polymer micelles at different temperatures was measured by the dynamic light scattering?DLS?.The influences of the length of the hydrophilic/hydrophobic block of the polymer and concentration of the solution on the micellization and gelation behavior were explored respectively.At certain concentrations,the polymer solution underwent a sol-gel phase transition to form in situ hydrogel due to it's temperature response.By adjusting the length of the hydrophilic/hydrophobic block of the polymer,or the concentration of the polymer solution,the goal of"sol at room-temperature and gel at body-temperature"can be achieved.In addition,due to the pH-sensitive and biodegradable of the polymer,the hydrogels forming from the polymer can release DOX sustainably in the weak acidic environment of the tumor site.