Synthesis And Performance Of PCL-b-PHEAA Amphiphilic Block Copolymer Micelles

Due to their particularity and diversity,the amphiphilic block copolymers can be self-assembled into nano-particles with different morphologies in selective solvents,which have potential applications in the fields of biomedicine and catalysis.In recent years,micelles with biodegradability,biocompatibility,and environmental responsiveness have become a hot topic of new functional polymers.Compared with the small molecules,the self-assembled micelles of the copolymers are more stable.The stable drug-loaded micelles can prolong the cycle time of the drug in the body,facilitate the delivery and release of the drug.Accordingly,the synthesis of amphiphilic block copolymers with specific structures facilitates the formation of micellar aggregates with stable structure and suitable particle size.In this paper,a novel amphiphilic block copolymer was synthesized by atom transfer radical polymerization(ATRP),the micellization behavior of the copolymer in aqueous solution and the drug loading/release properties were investigated.The main results are as follows:The PCL-b-PHEAA amphiphilic block copolymers were synthesized by ATRP,polycaprolactone was reacted with 2-bromoisobutyryl bromide(BIBB)firstly,and a bromine atom was introduced at the chain end to obtain PCL-Br as a macromolecule initiator for ATRP.The polymerization of hydroxyethylacrylamide(HEAA)was then initiated by PCL-Br to obtain the amphiphilic block copolymer PCL-b-PHEAA.The structures of initiator and copolymers were characterized by 1H-NMR and IR,the molecular weight and thermal properties were investigated simultaneously.The initiator has porous structure and the block copolymer is dense layered.The melt transition of the copolymer occurs at near 50 °C.Compared with PCL,the copolymer is divided into two stages of weight loss,thermal stability decreased.The copolymer was dissolved in tetrahydrofuran and dialyzed with a large amount of ultrapure water to completely remove the THF.The copolymers were self-assembled in aqueous solution to form spherical micelles.The critical micelle concentration(CMC),particle size and distribution were measured by fluorescence spectroscopy and laser particle size analyzer;the water contact angle measuring instrument was used to study the hydrophilicity;to visualize the morphology of these nanoaggregates,the samples were subjected to scanning electron microscope,transmission electron microscope analysis,the effects of different pH values on particle size and morphology were also studied.The results show that the copolymer was self-assembled into a stable micellar system by dialysis in the aqueous solution,which has obvious Dindal phenomenon.The water contact angle of the PCL is 56.5° and the copolymer solutions are in the range of 26~31°.In solutions with different pH results showed that the contact angle is small at pH=6.8,which indicate that the copolymer has obvious amphipathic.These amphiphilic block polymers were readily dispersible in water,and the average particle size of the copolymer PCL109-b-PHEAA14 micelles in the aqueous solution are 490 nm,which has a single peak distribution and good dispersibility.With the increase of pH value from 4.0 to 9.2,the particle size of micelles decreases and the polydispersity index does not change much.Scanning electron microscope showed that the morphology of 0.1 mg/mL micelles are sphere with good dispersibility.Under acidic conditions,the micelles always have a tendency to change from sphere to rod or sheet driven by crystallization.Transmission electron microscope(TEM)shows that the average diameter of spherical micelle are 104 nm.The critical micelle concentrations of the block copolymers PCL109-b-PHEAA32 and PCL109-b-PHEAA14 are 1.62 ?g/mL and 12.2 ?g/mL respectively.SEM images shows that the freeze-dried drug-loaded micelles are spherical with an average particle size of 564 nm.After standing for half a month,the stability of the drug-loaded micellar solution was decreased,the particle size increased significantly,and the polydispersity index increased.The release behavior of drug loaded micelles showed that the cumulative release in buffer was gradually increased with the passage of time.This biocompatible,biodegradable,newly designed PCL-based amphiphilic block nanocarriers has a potential applications in the field of biomedicines.