Hydrogel-based Molecularly Imprinted Polymers Prepared By Frontal Polymerization And The Application In Drug Controlled Release

Molecular imprinting technology(MIT)is a new method to synthesize materials with specific recognition ability.Stimulation-responsive hydrogels have demonstrated excellent application in various fields such as drug delivery.Hydrogel-based molecularly imprinted polymers(hydroMIPs)with stimuli-sensitive recognition toward target(template)molecules can reversibly swell and shrink in response to environmental changes.In the present work,frontal polymerization(FP)was successfully utilized to obtain pH/temperature-sensitive hydrogel-based molecularly imprinted polymers(hydroMIPs),and the effects of external environment and preparation conditions on the recognition ability of template was investigated.In the first part,hydroMIPs were synthesized by frontal polymerization using N-isopropylacrylamide(NIPAm)and acrylic acid as functional monomer,N,N’-methylenebisacrylamide as crosslinker,dimethylsulfoxide as porogen and gatifloxacin(GFLX)as template.The polymerization reaction can be completed in 20 min.The influence of template concentration and the crosslinker amount on the imprinting effect of the hydroMIPs was investigated.The gatifloxacin imprinted polymer formed in frontal polymerization displayed higher affinity and selectivity than conventional thermal polymerization.It can be seen from the results of the in vitro release experiments that the hydroMIPs prepared by frontal polymerization have strong temperature and pH sensitivity.The loaded FP-based hydroMIP was observed almost zero order release of GFLX with the long duration time(about 14 h).In vivo pharmacokinetic studies also show that FP-based hydroMIPs exhibit higher bioavailability compared to BP-based hydroMIPs.These results illustrate the potential of FP-based hydroMIPs as sustained release drug carriers.In the second part,hydroMIPs were synthesized by frontal polymerization using the deep eutectic solvent as porogen and thymopentin(TP-5)as template.The ratio of choline chloride to ethylene glycol in the deep eutectic solvent,the amount of cross-linker and template were investigated to optimize the preparation of hydrogel.Swelling behaviors and adsorption capacity of all hydrogels were measured.The optimum preparation conditions were as follows: the ratio of choline chloride toethylene glycol was 1:7,the degree of crosslinking was 1.4% and the amount of template was 0.48 mmol.The results of in vivo release study show that the FP-based hydroMIPs have an obvious sustained release effect of TP-5 and higher relative bioavailability in rat than BP-based hydroMIPs(FP-based hydroMIPs of 216.2%,BP-based hydroMIPs of 120.3%).In addition,MTT results show that all hydrogels present non-toxicity and good compatibility with cells.