Preparation And Characterization Of Thermosensitive Smart Hydrogel Drug Loading System Based On PNIPA

Drug delivery systems?such as micelles,nanoparticles,polymers,and liposomes?have been widely studied and applied in clinical experiments due to their ability to solve the side effects of poor water solubility,short half-life,low biocompatibility,rapid excretion and poor targeting in the process of drug use.In recent years,the intelligent drug delivery systems with stimulus responsive aroused people's interest and attention,especially intelligent drug delivery systems with temperature and magnetic response,which can use external magnetic fields to directionally deliver or guide drugs to diseased site,control the release on demand,reduce the number of medications,extend the effect time and achieve the best therapeutic effect.Therefore,in this study,two kinds of drug-loading systems were prepared by using biocompatible spherical mesoporous nanoparticles?and magnetic nanoparticles?as crosslinking agents.The factors influencing the drug-loading and drug-release capability were studied,which provided basic data for clinical application.1.Preparation and study of PNIPA/MSN composite hydrogel drug loading system: Mesoporous silica nanoparticles?MSN?were synthesized by Stober method,the specific surface area of MSN was 413.2 m2/g,and the average pore size was about 19.2 nm.Using MSN as cross-linking agent and KPS as initiator to polymerize NIPA,PNIPA/MSN composite hydrogels with a rich honeycomb structure was prepared.The DSC results showed that the addition of MSN did not change the thermosensitivity of composite hydrogels.The rheological analysis showed that the composite hydrogel appeared as viscous liquid before the lowest critical temperature LCST;After LCST,the phase of hydrogel changes to solid state,and the phase transition temperature was consistent with DSC results.In the experiment,bovine serum albumin?BSA?was used as a model drug to study the drug-loading capacity of the PNIPA/MSN composite hydrogels.The results showed that the loading capacity of BSA was increased with the increase of MSN content in the composite hydrogels.BSA,egg white lysozyme,and collagen oligopeptide were selected as model drugs of large,medium and small molecular weight to study the release properties of composite hydrogels in vitro.The results showed that the composite hydrogels had similar temperature sensitivity to the three model drugs,and could control drug release by adjusting the temperature regulation.The results of hemolytic experiments showed that the composite hydrogels had good biocompatibility.Therefor,PNIPA/MSN composite hydrogels were considered to be a drug controlled release carrier with good temperature-sensitive.2.Preparation and study of PNIPA/MSN-NH₂/PAA@?-Fe2O3 composite hydrogels drug loading system: In the drug delivery system,there is limited on the stimulus response only for temperature.In order to make hydrogel drug delivery system have more applications,PNIPA/MSN-NH₂/PAA@?-Fe2O3 composite hydrogel have been prepared.MSN-NH₂ was prepared by using ?-aminopropyltriethoxysilane to amination under acidic conditions.Under alkaline conditions,PAA@?-Fe2O3 was obtained by reacting ?-Fe2O3 with PAA.In the experiment,PNIPA/MSN-NH₂/PAA@?-Fe2O3 composite hydrogels?PNMPAFe-x?was obtained by using MSN-NH₂ and PAA@?-Fe2O3 as cross-linking agents,KPS was used as an initiator to polymerized NIPA.The zeta potential of nanoparticles indicated that the positively-charged MSN-NH₂??=25.8 m V?combined negatively-charged PAA@?-Fe2O3??=-48.86 m V?contributes to formation of PNMPAFe-x composite hydrogels with weak negative potential.The results of thermogravimetric analysis showed that compared with PNIPA/MSN,PNMPAFe-x composite hydrogels have one more thermal weight loss at 430 ?,which was caused by thermal decomposition of PAA on PAA@?-Fe2O3.The saturation magnetic moments of PNMPAFe-3 and PNMPAFe-6 are about 1.24 and 3.17 emu/g,respectively.The hysteresis loop of 300 K shows superparamagnetism property,and there was no remanence effect under low magnetic fields.The macroscopic experiments also showed that the composite hydrogels have good magnetic response.The swelling experiment showed that the PNMPAFe-x composite hydrogels had good swelling properties.Doxorubicin hydrochloride?DOX?was used as a model drug to study the drug loading capacity of PNMPAFe-x composite hydrogels.The results showed that the loading capacity basically increased with the increase of MSN-NH₂ and PAA@?-Fe2O3 content in the composite hydrogels,PNMPAFe-6 had the strongest drug loading capacity,and the encapsulation rate for DOX was 83.88 %.The drug release ability of PNMPAFe-x composite hydrogels was studied by centrifugation method,and the results showed that PNMPAFe-6 composite hydrogel was sensititive to temperature and could control the drug release time by adjusting temperature.The results of hemolytic studies showed that the PMNPAFe-x composite hydrogels had extremely low hemolytic activity,and therefore had excellent biocompatibility.The PNMPAFe-x composite hydrogels obtained by this experiment had thermosensitivity and magnetic sensitivity.It is expected to guide to the lesion site by magnetic field and release the drug through magnetocaloric effects,thus achieveing the purpose of synergistic treatment.