Preparation And Drug Controlled Release Properties Of N-Isopropylacrylamide Based Hydrogels

In the development of drug carriers,stimuli-responsive hydrogels with good tissue similarity and environmental sensitivity have effectively solved the problem that traditional drug carriers are difficult to deliver drug on demand.Among them,the hydrogel based on Nisopropylacrylamide(NIPAM)has the responsive temperature close to human body,which makes it especially suitable for the controlled release process under physiological conditions.At present,although there are many literatures regarding this kind of hydrogel,some problems such as complex preparation,single responsiveness and narrow application still remain to be solved.In view of this situation,a series of hydrogel materials based on NIPAM were designed and synthesized,which simplified the preparation process,introduced various kinds of stimulus responsiveness,and achieved the controlled drug delivery under different environmental conditions.The details were as follows:By using a unique ethanol/water mixed solvent,a homogeneous reaction system consisting of methacrylic acid(MAA)and NIPAM was constructed and then a dual-responsive hydrogel P(MAA-co-NIPAM)was successfully prepared through the classical free radical polymerization under mild condition.This kind of hydrogel possessed dense porous structure and good thermal stability,and could significantly respond to pH and temperature conditions.The volume phase transition temperature of the hydrogel was 35℃ close to body temperature.With doxorubicin(DOX)as a model drug for loading and in vitro controlled releasing,the highest drug loading efficiency could reach 95.68% and the drug releasing process could be well controlled by adjusting environmental conditions.The most appropriate kinetic model and mechanism to describe the releasing behaviors were Korsmeyer-Peppas model and Fick diffusion,respectively.Based on P(MAA-co-NIPAM),a triple-responsive multifunctional hydrogel PPy/P(MAA-co-NIPAM)was prepared by introducing polypyrrole(PPy)with near-infrared(NIR)responsiveness through in-situ polymerization.The photodeformable,photothermal and drug releasing ability of the hydrogel under NIR light control were explored.The results showed that PPy units were stacked on the polymer networks in the form of particles.After NIR irradiation,the hydrogel not only displayed the change of swelling ratios,but also achieved fast shape deformation and photothermal conversion within 60 s.Besides,NIR light could be considered as a ‘switch’ to control the drug releasing behavior of the hydrogel,which reflected its good light-operated characteristics.Finally,on the basis of the two parts above,chitosan(CS)with rich reactive groups was introduced to modify the hydrogel system for breaking the limitation of scale,resulting in the formation of a responsive nanogel CS/P(MAA-co-NIPAM)with the nanoscale.Dynamic light scattering showed that the hydration diameter of the nanogel in aqueous dispersion was only 145 nm at 45℃.The results of the performance test demonstrated that the hydrophilicity and hydration diameter of nanogel could be adjusted by changing pH and temperature conditions.Benefit from the unique advantages of its own scale,the nanogel had the possibility of administration through injection.Kinetic model fitting results confirmed that the change of environmental conditions not only influenced the drug releasing behavior of nanogel,but also affected its releasing mechanism.In conclusion,different kinds of hydrogel based on NIPAM were designed and prepared.P(MAA-co-NIPAM)hydrogel was prepared by using a unique mixed solvent system and the polymerization of immiscible monomers was achieved.Furthermore,PPy/P(MAA-co-NIPAM)hydrogel strengthened the control performance by integrating NIR responsiveness.CS/P(MAA-co-NIPAM)nanogel not only maintained the hydrophilicity and controlled release property of the hydrogel carrier,but also enriched the route of administration relying on its nanoscale.