A Preliminary Study On The Preparation Of PCL / PEG Amphiphilic Co - Network Polymer And PLGA As A Vaccine Carrier Based On Click Chemistry

Amphiphilic polymer conetworks (APCNs) have received considerable attention owning to their unique properties that conventional homopolymer-based hydrogels without. APCNs were two-component networks of covalently interconneted hydrophilic/hydrophobic (HI/HO) phase of cocontinuous morphology, which can swell both in water and organic solvent. APCNs were characterizad by three properities in structure:the coexistence of HI and HO segments, covalent linkages between the phases and phase cocontinuity. Inspired by their unique properties, numerous application studies have been focused on APCNs such as drug delivery matrices, cell culture surfaces, contact lens materials, nanoreactors, etc.Ring opening polymerization (ROP) of lactones have been investigated thoroughly over the last 40 years, due to its mild reaction conditions and efficient high yield. The molecular weight (MW) of polymers could be regulated by controlling the molar ratio of monomer and initiator. Click reactions, especially Huisgen 1,3-dipolar cycloaddition between azides and alkynes (CuAAC), has proved to be an effective method to prepare the well-defined APCNs because of its remarkable advantages, e.g., the high efficiency, quantitative yields, excellent functional group tolerance and mild reaction conditions. We designed a series of PCL/PEG based well-defined amphiphilic conetworks via the combination of ROP and click chemistry.First of all, a series of six-arm star-shaped poly(ε-caprolactone) (6-s-PCL) were synthesized by ring opening polymerization of ε-caprolactone using inositol as a multifunctional initior. And then 6-s-PCL was modified by 4-pentynoic acid to obtain ω-alkyne-terminated 6-s-PCL (6-s-PCL-C=CH).The structure of the polymers were demonstrated by FT-IR and 1H NMR. The MW and polydispersity index were tested by GPC, which showed that the MW of these polymers was unimodal and had good uniformity. Besides, azido-terminated PEG (N3-PEG-N3) was also successfully prepared.Moreover, a series of APCNs were obtained by click chemistry between 6-s-PCL-C= CH and N3-PEG-N3. The swelling degree of the APCNs were determined both in water and orignic solvent. The morphology and thermal behaviors of the APCNs were investigated by SEM and DSC respectively. The result indicated that there are many pores in the surface of APCNs and nanophase separation of hydrophilic and hydrophobic phases occured.Finally, the biodegradablity in vitro and biocompatibility of APCNs were evaluated. In addition, the release of PTX and DOX were investigated by using APCNs as carrier. The result of biodegradablity showed that the degradation rate of the APCNs were slower and WST-1 assay proved PCL/PEG APCNs has excellent biocompatibility. The amount of loaded PTX and DOX were affected clearly by the compositions of hydrophobic/hydrophilic phase. The higher the hydrophobic phase in the APCNs, the greater the amount of PTX loaded. Conversely, the higher of the hydrophilic phase in the APCNs, the greater the amount of DOX loaded. The release behavior of PTX and DOX in vitro revealed that the accumulate release PTX and DOX could be regulated by controlling the HO/HI composition in APCNs and the swelling degree of APCNs played a key role in the release rate of the drugs。In recent years, biocompatible and biodagradable polymers such as poly(D,L-lactic-co-glycolic acid) (PLGA) have been widely studied as one of the effective delivery systems for sustained release of antigens including proteins and DNA. However, the nanoparticles as vaccine vectors prepared by different arm-shaped PLGA are rarely repored. The main research content is as follows:Linear shaped PLGA (L-PLGA),3-arm star-shaped PLGA (3s-PLGA),4-arm star-shaped PLGA (4s-PLGA) and 6-arm star-shaped PLGA (6s-PLGA) were successfully synthesized by ring opening polymerization, then, OVA nanoparticles were prepared by using L-PLGA,3s-PLGA,4s-PLGA and 6s-PLGA respectively. Our study demonstrated that the four polymers all have favorable biocompatibility. The size of L-PLGA-OVA NPs,3s-PLGA-0VA NPs,4s-PLGA-OVA NPs and 6s-PLGA-OVA NPs were 319.5±22.2 nm,285.0±35.6 nm,270.6±8.0 nm and 282.1±32.1 nm respectively. Moreover, the encapsulation efficiency of the above mentioned nanoparticles were 19.0±2.4%,23.7±2.4%,27.8±1.1% and 29.5±2.2%. In vitro drug release experiment was carried out for 24 days.The result showed that burst effect exist and the release rate of OVA become slower with the polymer arms increase.