Synthesis Of Amphiphilic Polymer Via Macromolecular Degradation And Its Use In Drug Release

In recent years, bio-degradable polymer as drug carrier has attracted widespreadattention. Polycaprolactone and sodium alginate have attracted intense research interest asbio-degradable polymer drug carriers. They are artificially synthesized and natural degradablepolymer materials respectively. Based on their advantages and disadvantages, this work hasdone the following work:First, amphiphilic block copolymer of polycaprolactone-block-polyglycol wassynthesized via degradation method and micellar solution was obtained. The reactionmechanism is Nucleophilic substitution. Fourier transform infrared (FTIR) and NuclearMagnetic Resonance (NMR) analysis was conducted to characterized the composition andstructure of the polymer. The thermal properties of the copolymer were studied bythermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GelPermeation Chromatography (GPC) was conducted to analyze the molecular weight and itsdistribution. The florescence spectrum (FS) and transmission electron microscope (TEM)measurement were conducted to characterize polymer micelle. The results show that thismethod is very successful in the synthesis of lock copolymer ofpolycaprolactone-block-polyglycol. Its molecular weight, distribution, thermal properties,critical micelle concentration (CMC) and the micelle size are closely related with thepolycaprolactone (PCL) content. Its molecular weight, thermal properties and critical micelleconcentration (CMC) increased as the polycaprolactone (PCL) content increased.Second, the as-synthesized polycaprolactone-block-polyglycol and brufen were madeinto micelle. The effect of PCL content on encapsulation ratio, drug carrier ratio in phosphatebuffer was studied. The cell cytotoxity experiment was conducted to evaluate the toxicityeffect on human body. The nanoparticle size measurer and transmission electron microscopewere conducted to characterize the micelle drug morphology and size distribution. The resultsshow that encapsulation ratio and drug carrier ratio increased as the polycaprolactone (PCL)content increased. The drug release speed decreased in PBS buffer （0.05mol/L，KH2PO4-NaOH）. The cytotoxicity test show that the particles are nearly nontoxic and safe foruse. The micelle particle size distribution is uniform after drug loading. The particle sizeincreased about50nm after drug loading.Finally, the as-synthesized polycaprolactone-block-polyglycol was blended with sodiumalginate. Because the polymer is amphipathic, it can be well blended with sodium alginate toform a stable system. Then the blended solution reacted with calcium chloride throughcross-linking to form PCL-PEG/sodium alginate composite gel bead. Bovine serum albuminwas selected as drug model, the effect of polymer content on drug load ratio, encapsulationratio was studied. Its swelling behavior and drug release control ability are also studied. TGand DCS measurement were conducted to examine the thermal behavior of composite gel.Universal tester was used to analyze the mechanical behavior of the composite gel. SEM wasutilized to examine the surface structure of the gel beads after swelling in various solutions.The results show that encapsulation ratio and drug carrier ratio increased as the polycaprolactone (PCL) content increased. The drug release speed and swelling ratiodecreased in PBS buffer (pH=7.4). The SEM results show that the microbeads did not swell inhydrochloric acid (pH=1.2). The PBS buffer, the cavity structure would appear once themicrobead swelling took place. Sodium alginate and the blend system were made intomembrane cross-linked by calcium ions. The rim angle analysis shows that when PCL-b-PEGwas added, the rim angle increased and hydrophobicity was enhanced.