Study On Synthisis And Insulin Delivery Properties Of Multi-responsive Nanogel System

Nanogels,well known for their high water content,high specific surface area,good biocompatibility and high stability,are deemed to havepromising application prospect in drug delivery system.In this paper,multi-responsive nanogels were synthesized with microemulsion polymerization by using polyethylene glycol diacrylate(PEGDA)and PBDEMAEDMA as the cross-linkers,respectively.In addition,we gived an insight study on the mechanism of thermo-sensitive,pH-responsive,salt-tolerant and insulin delivery behavior.1.P(NIPAM-PEGDA-PBDEMA)nanogels with PBDEMA mol content of 2.75%,9.80%and 20.64%were synthesized by microemulsion polymerization using thermosensitive isopropylacrylamide(NIPAM)and sugar-responsive phenylboronic acid ester(PBDEMA)as monomer,PEGDA as a crosslinking agent and characterized by DLS and TEM.The results showed that the particle size have a narrow distribution in spherical form.The temperature-sensitive,salt-tolerant stability,drug-loading rate and sugar response of these nanogels were studied.The results found that with the increase of the content of phenyl borate,the critical dissolution temperature(LCST)of nanogels decreased,insulin loading rate and package rate increased.Furthermore,and the sensitivity to sugar concentration at physical salt concentration(0.15 M PBS pH 7.4)increased,and showed an excellent self-control insulin release behavior.2.PBDEMAEDMA,a novel crosslinker with dual responsive on pH and sugar,was designed and synthesized for the first time.Its chemical structure was characterized by 1H NMR,13C NMR and FT-IR.P(NIPAM-PBDEMAEDMA-PBDEMA)nanogels with PBDEMA and PBDEMAEDMA mol content of 2.80%,9.65%and 19.64%were prepared using this crosslinking agent,NIPAM and PBDEMA,and tested by NMR and DLS,which indicated that nanogel particle size distribution was uniform.The temperature sensitivity,salted stability,pH-response and sugar responsiveness of these nanogel were analyzed.Due to the introduction of PBDEMAEDMA,the LCST value of nanogels decreased compared with the P(NIPAM-PEGDA-PBDEMA)nanogels,and these nanogels were disintegrated under both acidic and glucose conditions since the acetal bond in PBDEMAEDMA broke and boron ester bond competed for the combination with glucose molecules,respectively,which resulted in double bond falling off from the PBDEMAEDMA,and the important role of crosslinker failed.Thus the sugar sensitivity of nanogel was improved to be faster than P(NIPAM-PEGDA-PBDEMA)nanogels with a distinguished degradation.