Preparation And Properties Of Multi-Crosslinked Pnipam Hydrogels

Injectable hydrogels are widely used in the field of topical medical materials,tissue engineering and drug delivery because of rapid in-situ cross-linking and their highly hydrate threedimensional porous structure which mimics biological tissues.Poly(N-isopropylacrylamide)(PNIPAM),possessing hydrophilic and hydrophobic groups,is a kind of temperature-responsive polymer.The lower critical solution temperature(LCST)of PNIPAM is about 32?,which is close to the body temperature.Injectable PNIPAM based hydrogels could be prepared via hydrazide-aldehyde crosslinking reaction,which can rapidly formate at room temperature.Hoevever,the network of hydrogel formed by hydrazone bonds is defective due to the short reaction time,results in a lack of strength.It has been confirmed that the strong physical crosslinking stem from the highly stable hydrogen bonded interaction domains formed among dual amide motifs in the side chain of poly(N-acryloyl glycinamide)(PNAGA).At the same time,PNAGA has good biocompatibility and a certain similarity with the chemical structure of PNIPAM.Hydrogen bonding cross-linking of PNAGA is introduced in order to improve mechanical property of hydrogels.Especially,without extra crosslinking agent,the hydrogen bond enhancement is simple and efficient,which is suitable for the preparation of biological materials.PNAGA was prepared by free radical solution polymerization,and then regulated the concentration of PNAGA aqueous solution to ensure it was liquid at room temperature.The dilute aqueous solution was mixed with dextrin oxide and the hydrazine of PNIPAM,and then co-injected at room temperature to acquire a seriers of PNIPAM-based thermosensitive hydrogels enhanced by PNAGA.The main works of the thesis are as follows:1.Preparation and characterization of PNAGA.N-acryloyl glycanamide(NAGA)was prepared by the reaction of acryloyl chloride and glycinamide hydrochloride.PNAGA was prepared by free radical solution polymerization with NAGA as the reactive monomer,azobisisobutylphosphonium hydrochloride(AIBA)as the initiator.Influences of pH and reaction temperature on the polymerization of PNAGA were investigated.The structure,molecular weight and distribution of PNAGA were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography.Results showed that the suitable temperature for free radical solution polymerization of NAGA(with AIBA as initiators)was 60? and the pH was about 5-6;the number average molecular weight of PNAGA was about 240,000 g-mol-1,and the molecular weight distribution was 1.32.2.Preparation and characterization of PNIPAM based thermosensitive hydrogel enhanced by PNAGA.The target hydrogel was prepared by co-injection with the dextrin oxide and the hydrazine of PNIPAM as raw materials,the low concentration PNAGA aqueous solution(?1.5%)as the enhancer.The morphology and properties of the target hydrogel were studied.(1)The internal morphology of the hydrogel after freeze-drying was observed by scanning electron microscope.The polymer remaining after the water removed from the hydrogel showed a network porous structure,and the internal pore diameter of the hydrogel enhanced by PNAGA was significantly smaller than that of the unreinforced hydrogels.(2)The dynamic modulus of the hydrogel was characterized by the parallel plate rheometer.The dynamic modulus of the hydrogel prepared with different mass fractions of PNAGA aqueous solution was investigated.The dilute solution of PNAGA(mass fraction?1.5%)can reinforce the PNIPAM-based aldoxime cross-linked hydrogels with a maximum storage modulus up to 517.0 kPa,and that was five times that of unreinforced hydrogels(90.2 kPa).(3)Temperature-sensitive property of hydrogels was studied and rusult showed that hydrogels exhibited good temperature-sensitivity in PBS buffer at alternating cycle temperatures of 25? and 37?.(4)The study of the cross-linking performance of hydrogel under acidic conditions showed that the higher the acid concentration of the system is,the faster the cross-linking.De-crosslinking time of composite hydrogel increased due to the existence of PNAGA.(5)?-adrenoceptor blocker(propranolol hydrochloride)was loaded on hydrogel,and its drug release property was studied.The drug release rate of hydrogel enhanced by PNAGA was slightly faster than that of the unreinforced hydrogels,and slow down with increasing drug concentration,drug release time is lasted than 10 days,drug release amount of hydrogels more than 90%.