| In recent years,the pollution of the atmosphere,soil and water caused by the extensive use of antibiotics or the misuse of antibiotics has become a new type of ecological environmental pollution.Due to the slower rate of biodegradation of antibiotics in the body,a large number of antibiotics enter the body after injection,oral administration or as a feed additive,and then enter the environment mainly in the form of metabolites or excretions in the form of feces or urine.In the end,the development of human society is ultimately affected by the environment.The emergence of new biomaterials has made it possible to obtain new veterinary antibiotics that are highly efficient,easily absorbed,and rapidly degradable.At present,biodegradable biomaterials are used as controlled-release encapsulation materials for antimicrobial drugs to produce drug-loaded microspheres for sustained drug delivery and localized delivery,improve drug delivery efficiency and bioavailability,prolong residence time in the body,and reduce pollution.The strategy of creating huge economic benefits has received widespread attention.In this paper,this chitosan quaternary ammonium salt was synthesized by N-2-hydroxypropyl trimethyl ammonium chloride chitosan(N-2-HACC),and N-2-HACC as amoxicillin delivery carrier,load polyelectrolyte compound preparation of amoxicillin N-2-HACC nanoparticles(N-2-HACC/CMC/AMX NPs),and we discusses the antibacterial mechanism of the N-2-HACC/CMC/AMX NPs.The test results show that:(1)N-2-HACC was successfully prepared,and the cytotoxicity test results showed that the toxicity of the N-2-HACC to 293 T cells was small,indicating that N-2-HACC was a safe delivery carrier with good biocompatibility.(2)The preparation process of N-2-HACC/CMC/AMX NPs was determined,the concentration of N-2-HACC was 1.0mg/mL,CMC concentration was 2.5mg/mL and amoxicillin concentration was 0.5mg/mL.(3)The preparation of N-2-HACC/CMC/AMX NPs is round,dispersive and smooth,with an average particle size of 319.5±67.0 nm,Zeta potential is +57.25 ±0.46 mV,the encapsulation rate is 88.84±0.52%,and the drug load is 44.6±0.41%.(4)In vitro release test results showed that amoxicillin N-2-HACC nanoparticles had obvious slow release characteristics.(5)Stability test results show that N-2-HACC/CMC/AMX NPs can be stored for long-term storage at 4?,-20? and room temperature;(6)The experimental results in mice showed that the N-2-HACC/CMC/AMX NPs was released slowly in mice after single administration,and the absorption degree was high after the injection.The average residence time of drugs(MRT)was 6.81±0.48 h,drug half-life(t1/2)was 4.70±0.30 h,apparent volume of distribution(Vz/F)was 0.05±0.003 mg/ug/mL,total clearance(Cl/F)was 0.006 ±0.0002 mg/ug/mL/h,relative bioavailability F = 321.14±13.15%.(7)Bacteriostatic test results show that N-2-HACC of Escherichia coli,Acinetobacter baumannii,Streptococcus pneumoniae,and Staphylococcus aureus has the inhibition,the cooperative use of amoxicillin and significantly enhances the inhibition of bacteria.(8)The antibacterial mechanism test results show that the N-2-HACC/CMC/AMX NPs can be combined with a bacterial protein on the cell membrane,destroying bacteria cell membrane integrity,affect the normal physiological activity of bacteria,eventually killing bacteria burst.This study has important practical significance for solving and promoting the useof key technologies such as residues of veterinary antibiotics,environmental pollution,and slow release and release.It has important practical significance in promoting the upgrading of veterinary antibiotic products and industrial technological progress.Simultaneously,this project is promoting scientific and technological progress.Protecting the ecological environment,ensuring the healthy development of modern livestock and poultry husbandry,and improving people's material and cultural life and health standards will all play an important role.Economic and social benefits are enormous. |
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