Preparation And Properties Of Amino Acid Based Drug Loaded Hydrogel Dressing

Wound healing is a slow and complex process affected by many factors.The appearance of wound dressing brings hope for the rapid and infection free treatment of wounds.In recent years,hydrogel wound dressings have attracted great attention as a new dressing.However,single component hydrogel dressing can not be applied to more different types of wounds,it may be stimulated by complex external environment of wounds in a slow recovery process.Then,the recovery time would be extended.Natural macromolecule hydrogels lack certain mechanical properties,while polymer gels are biocompatible.Therefore,the modified amino acids and their derivatives are used as functional monomers to prepare polymeric hydrogels with different chain structures.Different anti-inflammatory drugs are loaded in synthetic hydrogels in different ways to get functional anti-inflammatory hydrogel dressing,and their comprehensive properties can be adjusted to get better hydrogel dressing.1.In order to prepare a physically crosslinked hydrogel dressing with good biocompatibility and controlled release,the amino acid monomer N-acrylglycineamide（NAGA）and the biological fermentation product itaconic acid（IA）were used as monomers,and the temperature was constant at 65 when ammonium persulfate was used as initiator.Under the condition of temperature,free radical polymerization was used to form hydrogel poly（N-acryloyl glycine amide-itaconic acid）（P（NAGA-IA））without adding any crosslinking agent.The four groups of hydrogels with different properties were obtained by adjusting the molar ratios of different monomers.The hydrogels were physically blends and loaded with tetracycline hydrochloride to obtain drug loaded hydrogels through their phase transition behavior（P（NAGA-IA）@TC）.The structure of NAGA and copolymer P（NAGA-IA）were measured by IR and NMR.The molecular weight of the obtained hydrogel was tested.The average molecular weight of the obtained hydrogel was more than 1×10⁵.With the higher the molar ratio of NAGA,the larger the molecular weight of the copolymer,the maximum was3×10⁵.Testing the mechanical properties of the four groups of hydrogels,we know that P(NAGA₂₀-IA₁)has the highest tensile strength and up to 0.67 MPa,and its tensile strength is nearly 10 times higher than that of P（NAGA₇-IA₁）.P(NAGA₂₀-IA₁)has the highest compressive strength and can reach 540 k Pa,which was nearly 10 times higher than that of P（NAGA₇-IA₁）.It was found that the time of release about P（NAGA-IA）@TC was shorter than that of neutral condition when p H was alkaline,and the release rate of the experimental group was better than that of neutral condition.The release period was up to 3 days.In addition,the antibacterial effects of four groups of gels were tested.P（NAGA-IA）@TC could achieve 99%antibacterial activity against Escherichia coli and Staphylococcus aureus after 3 h cultivation.The results of cytotoxic tests showed that the activity of P（NAGA-IA）and P（NAGA-IA）@TC1%was over 80%after the total culture of L929 mouse fibroblasts for 3 days.Therefore,the obtained P（NAGA-IA）hydrogel could be used as wound dressing for wound healing.2.In order to further solve the cytotoxicity of hydrogels and long-term immersion in normal saline,there will be a phenomenon of dissolution.Acrylglycine（ACG）,acronyl-L-arginine（AARG）were synthesized by using acryl chloride,glycine and L-arginine respectively,and then they were polymerized with NAGA deionized water and a small amount of BIS was added.Using five homopolymers and copolymers of modified monomers as carriers,the drug loaded hydrogels（P（NAGA_x-ACG_y-AARG_z）@Le）were loaded by an anti inflammatory drug levofloxacin.Through rheological tests,the five groups of gel are stable viscoelastic solids.Among them,homopolymer hydrogel with multiple hydrogen bonds（NAGA,ACG）has higher modulus and lower modulus of copolymer hydrogel.The swelling rates of five groups of gels were determined.It was found that the swelling rates of five groups of gels were lower than800%,and physical crosslinking and chemical crosslinking stabilized the three-dimensional network structure of hydrogels.Under neutral p H,the release period of P（NAGA_x-ACG_y-AARG_z）@Le was found to be about 3 days,which had a certain release effect.Through the antibacterial test,P（NAGA_x-ACG_y-AARG_z）@Le can reach 90%antibacterial property after 6hours of cultivation with E.coli and Staphylococcus aureus,and the antibacterial effect is good.After testing the cytotoxicity of five groups of gels,it was known that P（NAGA_x-ACG_y-AARG_z）and P（NAGA_x-ACG_y-AARG_z）@Le had higher cell viability than those of L929 mouse fibroblast cells after 3 days,and the cell viability of the first day was about 130%.Therefore,the obtained P（NAGA_x-ACG_y-AARG_z）@Le hydrogel could be used as wound dressing for wound healing.In summry,Amino acids and their derivatives are copolymers constructed from functional amino acids.After loading different anti-inflammatory drugs,functional hydrogel dressing can be obtained,which can be used for loading anti-inflammatory drugs and drug release,so as to achieve trauma treatment.