| Objective:In order to improve the inhibitory effect of allicin on gastric cancer cells and prolong the gastric retention time,a gastric retention shape memory poly(lactic acid)/sodium carboxymethyl cellulose composite membrane delivery system loaded with allicin nanoparticles was constructed.Method:Biocompatible materials such as chitosan,soybean lecithin,polylactic acid(PLA),sodium carboxymethyl cellulose(CMC)and sodium carbonate were selected.According to the physiological characteristics of the stomach and the physical and chemical properties of the medical excipients,a delivery system was constructed which could stay in the stomach for a long time,release the drugs at an appropriate speed and significantly reduce the toxic and side effects.The delivery system also has the advantages of improving drug efficacy,reducing drug taking times,increasing patient compliance,reducing drug use cost,and producing better social and economic benefits.Using encapsulation rate and cumulative release rate as evaluation indexes,the formulation of allicin phospholipid-chitosan nanoparticles with the highest encapsulation rate and cumulative release rate was screened out.Using solvent injection method to prepare phospholipid-chitosan nanoparticles,observing the morphology and particle size of the nanoparticles,at the same time measuring and calculating the encapsulation rate of the drug-loaded nanoparticles,the methodological investigation and the drug release rate in vitro.Exploring the in vitro drug release of the composite membrane in simulating drug-loaded phospholipid-chitosan nanoparticles in gastric juice;observing its degradation performance and floating performance;using egg membrane to evaluate the mucosal adhesion ability of the composite membrane;testing the shape memory function of the drug-loaded composite film;using optical microscope,spiral micrometer and nanometer inspection microscope to observe the surface morphology of the composite film;using Fourier Infrared Spectrometer to identify the structure of allicin-phospholipid-chitosan nanoparticleloaded composite membrane;performing Differential Scanning Calorimetry(DSC)and mechanical performance tests on composite membranes;using CCK8 experiment to evaluate the in vitro cell survival rate of the shape memory polylactic acid/sodium carboxymethyl cellulose composite film on human gastric cancer cell SGC 7901 with and without drug loading.In this way,it is judged whether the 9 kinds of composite membranes have inhibitory effects on gastric cancer cells.Results:The formulation of allicin-phospholipid-chitosan nanoparticles for preparing nanoparticles was as follows:allicin 10 mg,lecithin 200 mg and chitosan 10 mg.The encapsulation efficiency of allicin-phospholipid-chitosan nanoparticles prepared by this formulation was 87.89%.Methodological investigation:the RSD value of the stability test is 0.29%,the RSD value of the precision test is 0.47%,and the RSD value of the repeatability test is 0.67%;Sample recovery test:the average recovery rate is 96.04%,and the RSD value is 1.75%.The cumulative release rate reached 65.04%at 24 h,and the release index was 0.20,which was less than 0.45,indicating Fickian diffusion.In the study of in vitro release,it was found that the drug-loaded nanoparticle/PLA-CMC solution composite membrane had the highest cumulative release rate compared with the other two composite membranes,reaching 35.31%in 9 h.The degradation rates of drug-loaded nanoparticles/PLA-CMC double-layer composite film,drug-loaded nanoparticles/PLA-CMC powder composite film,and drug-loaded nanoparticles/PLA-CMC solution composite film in simulated gastric juice for 9 h were 68.25%and 32.25,respectively.%,56.64%,and all have floating phenomenon.The adhesion evaluation and shape memory function test of the three composite films found that they have a certain degree of viscosity and deformability.Observing the surface shape and thickness of the six composite films through optical microscope,spiral micrometer,and nanometer inspection microscope,it is found that the distribution of nanoparticles is not obvious,and the thickness is in the range of 8.8 ± 0.03μm-25.0 ± 0.08 μm.The composite film infrared absorption spectroscopy analysis showed that the loading of drug-loaded nanoparticles had no effect on the chemical structure of the polymer.The transition temperature of the composite film is 57.95-64.98℃ tested by differential scanning calorimetry,and the lower transition temperature is conducive to the development of the composite film.The test of the mechanical properties of the composite film showed that the Young’s modulus of PLA film was 22.12 MPa,the tensile strength was 62.30 MPa,and the elongation at break was 5.44%;the Young’s modulus and tensile strength of the CMC film were 1.93 and 3.39 MPa;The Young’s modulus of PLA-CMC composite film is the smallest,which is 1.38 MPa,the tensile strength is 7.2 MPa,and the elongation at break is 8.63%.The presence of CMC has a certain effect on the rigidity of PLA,so adjusting the form of CMC and the ratio of PLA can control the rigidity of PLA.In the CCK8 experiment,it was found that PLA-CMC double-layer composite membrane,PLA-CMC double-layer blank nanoparticle composite membrane;PLA-CMC powder composite membrane,PLA-CMC powder composite blank nanoparticle composite membrane;PLA-CMC solution composite membrane,PLA-The composite membrane of CMC solution loaded with blank nanoparticles is not cytotoxic,and the composite membrane will not affect the proliferation of SGC 7901 gastric cancer cells.However,the double-layer drug-loaded nanoparticle composite membrane of PLA-CMC,powder drug-loaded nanoparticle composite membrane of PLA-CMC and solution drug-loaded nanoparticle composite membrane of PLA-CMC had obvious inhibitory effect on the proliferation of SGC 7901 gastric cancer cells due to the drug-loaded nanoparticle composite membrane. |
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