Preparation Of Polymeric Hollow Microspheres/Complex Micelles Based On Natural Polymer For Drug Loading And Controlled Release

In recent years,cancer has become the main causes for human death with the increase of incidence.Drug treatment is one of the most important methods to treat cancer.However,many anticancer drugs were limited due to many drawbacks,such as the instability,low efficiency and side effects.At present,the research of intelligent drug carrier is the important elements that reduce the drugs side effects and improve the treating effect.Compared with the conventional drug treatment,intelligent drug carrier has some unique superiority including good stability,excellent permeability,long cycle,targeting and environmental sensitivity.Natural polymers(SA?CS)also have been attracted extensive attention due to many advantages,such as good biocompatibility,degradation characteristics,non-toxic and cheap etc.?-CD,PEG and?-caprolactone also have advantages of safety,biocompatibility and degradation characteristics,so they has been widely applied in medical field.In addition,the ?-CD possess a unique hydrophilic surface and a hydrophobic inner cavity.It not only can contain various substances,but also can used to design inclusion complexes via host/guest inclusion with various compounds.In this paper,the graft copolymer(SA-g-PNIPAM,CS-g-CD)and the block copolymer(PEG-b-PCL)were prepared based on SA,CS,NIPAM,?-CD,PEG,?-caprolactone as raw materials.Sensitive polymeric micelles and hollow spheres were formed in aqueous solution by host-guest inclusion interactions or electrostatic interactions between positively charged and negatively charged.The contents of this paper are summarized as follows.1.The graft copolymer of sodium alginate-graft-poly(N-isopropylacrylamide)(SA-g-NIPAM)was synthesized by employing free radical polymerization.Light transmittance analysis showed that the graft copolymer has good temperature sensibility.The polymeric micelles were prepared by biocompatible SA-g-PNIPAM and divalent metal ions(Ba2+,Zn2+,Co2+)for controlled release of 5-fluorouracil(5-FU).Transmission electron microscopy(TEM)and laser particle analyzer showed that the polymeric micelles had a core-corona structure with good polydispersity.The polymeric micelles were observed as excellent performance on drug entrapment and release ability.Decreasing pH or increasing temperature and ionic strength of the solutions,a faster drug release rate was observed.2.The pH sensitive graft copolymer chitosan-grafted-?-cyclodextrin(CS-g-CD)was prepared based on chitosan and ?-cyclodextrin.The polymeric hollow spheres self-assembled from CS-g-CD and sodium tripolyphosphate(TPP)were prepared for controlled release of doxorubicin(DOX).The assemblies were formed by electrostatic interactions between positively charged amino group in CS-g-CD and negatively charged phosphate in TPP.When the weight ratio of CS-g-CD to TPP was 1:2,the light transmittance of hollow spheres was the best.The hollow spheres with diameters about 80 ~ 100 nm were confirmed by TEM and laser particle analyzer.The polymeric microspheres with hollow cavity were beneficial to improve the drug loading capacity for DOX.The cumulative release of DOX from CS-g-CD/TPP hollow microspheres increased with the decrease of pH and the increase of temperature or ionic strength.3.The amphiphilic block copolymer PEG-b-PCL was prepared based on the hydrophilic polyethylene glycol(PEG)and the hydrophobic ?-caprolactone as raw materials.The stimuli-sensitive CS-g-CD/PEG-b-PCL complex micelles as drug carrier were obtained via hydrophobic inclusion interactions between CS-g-CD and PEG-b-PCL.When the weight ratio of CS-g-CD to PEG-b-PCL was 1:2,the light transmittance of complex micelles was the best.The TEM figure showed that the polymeric complex micelles had the spherical structure with good dispersity and diameters about 60 ~ 90 nm.Release studies showed that the CS-g-CD/PEG-b-PCL complex micelles had excellent performance on drug entrapment and release ability.The cumulative release of DOX from complex micelles increased with the decrease of buffer solution pH and the increase of the temperature or ionic strength.