Preparation and Properties of Novel Liquid Crystal Molecularly Imprinted Sustained or Controlled Release Materials

Author:Zhang Li Ping

Supervisor:huang yan ping

Database:Doctor

Degree Year:2019

Download:19

Pages:160

Size:10900K

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Molecularly imprinted polymer(MIP)is a novel material that could select and recognize target molecules specifically.And Liquid crystal molecularly imprinted polymer(LC-MIP)is a polymer that can recognize the target molecule specifically at the low crosslinking level by replacing partly or all chemical cross-linker by liquid crystal monomer in the synthesis process of MIP.Therefore,the LC-MIP could maintain the stable structure with the rigid mesogenic units of liquid crystal and solve the problem of low imprinting efficiency of traditional MIP.Moreover,the LC-MIP as a drug release material can effectively improve the drug delivery characteristics,prolong the drug release time and increase the amount of drug load.In this thesis,four kinds of LC-MIP were prepared by combining the advantages of LC monomers and the applications in drug delivery systems were also investigated.The results were as follows:In the first part of thesis,MWCNT@LC-MIP was prepared by the LC-MIP grafted onto the surface of multi-walled carbon nanotubes(MWCNT),and the performance was evaluated as drug sustained-release carrier.By optimizing the synthesis conditions,the best content of cross-linker was 40% and the ratio of template to functional monomer was 1:4.The results showed the better binding effect on the levofloxacin(LVF),and the imprinting factor was 4.06.In vitro release of LVF-loaded MWCNT@LC-MIP was determined.Comparing with MWCNT@MIP,MWCNT@NIP and bare MWCNT,the LVF from the MWCNT@LC-MIP exhibited 3.8 μg/h of the release rate duration over 20 h.The results in vivo pharmacokinetic studies showed that LVF loaded by MWCNT@LC-MIP had the highest bioavailability(578.9%),which was 10 times and 50 times of the MWCNT@MIP and MWCNT respectively.This would provide a new method for the preparation of gastric retention floating preparations.In the second part of thesis,the paclitaxel molecularly imprinted polymers(LC POSS MIPs)were prepared by using LC monomer and polyhedral oligomeric silsesquioxane(POSS)as co-monomers.Compared with LC POSS-free MIPs,POSS LC-free MIPs and conventional MIPs,the imprinting effect was greatly improved when POSS and LC monomers were used together,which confirmed that the effect of POSS and LC monomers on imprinting was synergistic.The optimum synthesis conditions for LC POSS MIPs were that the content of POSS was 44.4%,MPDE selected as liquid crystal monomer and the ratio of template to functional monomer was 1:5.In this condition,the LC POSS MIPs had the greatest imprinting factor was 3.67 ± 0.11.The in vitro release study of LC POSS MIPs loaded with PTX confirmed that the LC POSS MIPs had a good controlled release effect on PTX.MTT assay showed that the LC POSS MIPs,the control group,LC POSS NIPs,LC POSS-free MIPs,POSS LC-free MIPs and conventional MIPs had good biocompatibility.The in vivo pharmacokinetic study proved that the LC POSS MIPs exhibited the highest relative bioavailability,which provided a new method for the application of PTX in oral administration system.In the third part of thesis,the metal-organic framework HKUST-1 was synthesized at room temperature,and the HKUST-1@LC-MIP was prepared by the LC-MIP coated on HKUST-1.By optimizing synthesis conditions,the AM selected as the optimal functional monomer,the ratio of template to functional monomer was 1: 2 and the content of MPDE was 40%.The equilibrium adsorption studies showed that HKUST-1@LC-MIP had a specific binding effect on the CAPE.By observing the morphologies before and after soaking in aqueous media,the HKUST-1@LC-MIP and HKUST-1@LC-free MIP could float on the media and remain at least 24 h.By contrast,the HKUST-1 sank immediately.Then,the X-ray diffraction(XRD)was tested further.Compared to all the HKUST-1 changed into unknown phase,the HKUST-1@LC-MIP showed no significant change being soaked in different media.The in vitro release of CAPE-loaded HKUST-1@LC-MIP was proved that HKUST-1@LC-MIP could control release CAPE at a constant rate over 11 h only,by comparing with the HKUST-1@LC-NIP,HKUST-1@LC-free MIP,HKUST-1 and commercial CAPE tablets.Finally,the in vivo pharmacokinetic study showed the HKUST-1@LC-MIP had the higher relative bioavailability.The results would lay a good foundation for the study of CAPE sustained and controlled release carrier in the future.In the four part of thesis,MIP without chemical cross-linker was prepared by combining immobilized template and liquid crystal monomer with HQN as template,QN as immobilized template,and MPDE as liquid crystal monomer.By optimizing synthesis conditions,the best content of MPDE was 52.9%,the ratio of template to functional monomer was 1/10 and the ratio of template to immobilized template was 8/5.The equilibrium adsorption studies showed that MIP had a specific binding effect on the HQN,and the imprinting factor was 3.44 ± 0.25.In addition,the adsorption effect of MIP on HQN and its analogues QN,HQND and QND proved that the MIP had specific recognition effect on HQN only.