Structure Design And Application Of Long-acting Drug-releasing Hydrogels

The traditional application of hydrogels as drug carriers always presents a slower response rate and transient efficacy,which greatly limits the range of applications for drug-controlled release hydrogels.In order to prepare hydrogel drug carriers with long-term drug sensitivity,a variety of hydrogel drug carriers with long-acting drug sensitivity were prepared through structural design,including the preparation of semi-interpenetrating networks using free radical copolymerization methods.Poly(HEMA/PVP)hydrogels and instant PNIPAAm/NPAAm/NVP hydrogels,as well as polymerizable and capped ZnS composite nanohydrogels,were designed for these three different structural hydrogels as iodine and epigalloctones.The use of catechin gallate(EGCG)and daunorubicin hydrochloride(DNR)drug carriers in the controlled release system of drugs has done the following significant work..First,2-hydroxyethyl methacrylate(HEMA)was selected as the main component network by radical copolymerization method,poly(N-vinylpyrrolidone)was the interpenetrating network,and azobisisobutyronitrile was used as the initiator to design and prepare the interpenetrating network structure.glue.The compatibility of the gels was analyzed by differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR).The hydrogels all exhibited a glass transition temperature(Tg),indicating that HEMA and PVP have a certain degree of miscibility.The mechanical testing of the hydrogel using a universal tester showed that the tensile strength of the hydrogel decreased with the increase of the components of the PVP content.The microscopic morphology of the hydrogel has a great influence on its performance,so the microscopic morphology of the pHEMA/PVP hydrogel was investigated by scanning electron microscopy(SEM).The photographs show different densities in different regions of the polymer.The surface of the pHEMA/PVP hydrogel obtained by heat treatment is smooth and no pores are observed.DSC and thermogravimetric analysis(TGA)were used to study the lower critical solution temperature(LCST)and thermal stability of pHEMA/PVP hydrogels.LCST increased slightly with the increase of PVP content,while its thermal stability increased with the increase of PVP content.The swelling kinetics of pHEMA/PVP hydrogel shows that the initial swelling degree of pHEMA/PVP hydrogel in water can fit the Higuchi equation well.The addition of PVP network in pHEMA hydrogels improves the diffusion of water in hydrogels..Secondly,three different drugs including iodine,EGCG and DNR were used as model drugs.The drug susceptibility of pHEMA/PVP hydrogel and drug release behavior as a drug carrier were investigated.For iodine,the pHEMA/PVP hydrogel impregnation solution is lighter than the pure pHEMA hydrogel.The fold increase in iodine loading in the pHEMA/PVP hydrogel was higher than in the pure pHEMA hydrogel.The combination of crosslinked PVP networks helps to increase the sensitivity of the hydrogel to iodine loading.By increasing the PVP content in the hydrogel,the release rate of the loaded iodine also decreases.From the release profile of iodine for up to 30 days,there is no positive correlation between the release rate and the amount of PVP network in the hydrogel.For EGCG,as the number of loading cycle increases,the color of the hydrogel gradually deepens,and the hydrogel volume shrinks to varying degrees.The addition of PVP network doubled the drug loading of the gel.With the increase of PVP content,the EGCG loading of each hydrogel increased in turn.With the same load of drug cycles,the difference between the water content of the hydrogel and the water content of the loaded drug increases with the increase of the PVP content of the pHEMA/PVP hydrogel.With the increase of the number of loaded drug cycles,the water content of the drug-loaded hydrogels decreased to varying degrees.The release of EGCG from hydrogels with different PVP content is different.As time progresses,the release rate slows and the amount of release gradually increases.Compared with the pure pHEMA hydrogel,the hydrogel containing PVP greatly avoids the violent release of EGCG drugs.The more PVP content is,the stronger the inhibitory effect is.In addition,pHEMA/PVP hydrogels coated with EGCG can effectively control the release rate of EGCG,enabling EGCG to achieve zero-order release without burst release in vitro.However,during the 75-day release experiment,the overall drug release was low and the highest cumulative drug release was only 48.5%of the total drug load.For daunorubicin hydrochloride,as the number of loading cycle increases,the color of the hydrogel gradually deepens,the color of the gel gradually assumes the color of DNR,and the volume of the hydrogel shrinks to varying degrees.With the increase of PVP content,the DNR loading of each hydrogel increased in turn.Compared with pure pHEMA hydrogels,pHEMA/PVP hydrogels have higher unit drug loading,which is 2~3 times more than the unit load of pure pHEMA hydrogels.With the increase of PVP content in the gel,the unit drug loading in the gel showed different degrees of increase.With the same amount of drug loading,the volume change of hydrogel increases with the increase of PVP content in pHEMA/PVP hydrogel.The release profile of DNR from hydrogels with different PVP content was similar,but the release rate was different.As time progresses,the release rate slows and the amount of release gradually increases.In the 35-day drug release profile,the PVP-containing hydrogel failed to avoid the drastic release of the DNR drug compared to the pure pHEMA hydrogel..Again,select N-isopropyl acrylamide(NIPAAm)as the main structural component,N-n-propyl acrylamide(NPAAm)as the second component,and vinyl pyrrolidone(NVP)as the third component.Potassium sulphate(KPS)is an initiator,and tetramethyl ethylene diamine(TEMED)is used as an accelerator to prepare the instant hydrogel by radical copolymerization.The product was detected by ~1H NMR.The thermal response behavior and light transmission of the copolymer solutions were tested in the absence and addition of daunorubicin hydrochloride.DNRs were embedded in NIPAAm/NPAAm/NVP hydrogels and released in distilled water,1 mg/mL,and 2 mg/mL EGCG solutions,respectively.The results showed that the lowest linking solution temperature(LCST)of the hydrogel was about 32°C,while the LCST of the gel with DNR was about 33°C.The hydrogel solution has lower light transmittance at UV-visible light 600 nm and lower temperature than LCST,while the DNR-loaded gel has higher light transmittance,which is up to 95%.In the three different release media,the release of DNR was faster at the initial stage of release.As time went by,the release rate slowed down and the amount of release gradually decreased.EGCG inhibited the release of DNR.The higher the concentration of EGCG,the stronger the inhibition of DNR releases,and there was no sudden release of DNR release in EGCG solution.Finally,a novel polymerizable group seal was designed and synthesized by chemical bonding between hydroxyl groups on the surface of ZnS(ME-blocked)and isocyanate groups of polymerizable 2-isocyanatoethyl methacrylate.Then ZnS NP was copolymerized with 2-Hydroxyethyl methacrylate(HEMA)monomer and N,N-dimethyl acrylamide(DMA)to design and prepare a high refractive index hydrogel with high content of inorganic and organic ZnS NPs.glasses.Increasing the ZnS content of the polymerizable group in the hydrogel increases its RI value and mechanical properties,whereas it’s light transmittance,equilibrium(ESR),and deposition of lysozyme on the hydrogel surface are slightly reduced.The ZnS-containing hydrogel has good cell compatibility and biocompatibility in vivo in rabbit eyes,indicating that it can be used as a high refractive biomaterial.EGCG was released as a model drug in composite nanohydrogels for up to 11 days,but drug bursts could not be avoided.The ZnS content in the hydrogel is high or low,and EGCG has similar release behavior.The release curve is divided into two parts,the preceding release zone and the sustained release zone.In summary,the three types of hydrogel pHEMA/PVP hydrogels,PNIPAAm/NPAAm/NVP hydrogels and polymerizable and capped ZnS nanocomposite hydrogels designed in this thesis are expected to be used as carriers for controlled release of long-acting drugs.