| Fatty acids are carboxylic acids with long hydrocarbon chains,which are organic compounds composed of carboxyl groups and carbon chains.Fatty acid vesicles are self-assembled aggregates formed by fatty acid and its salt solution near pKa with spherical structure of double-layer membrane.Fatty acid vesicles are a kind of natural biological material,which have the advantages of good biocompatibility,low cost and easy self-assembly in aqueous solution.The formation and stability of fatty acid vesicles are highly dependent on experimental conditions,such as ionic strength,pH and temperature,thus limiting their application.In this work,the anionic surfactant sodium oleate(SO)and polysaccharide sodium carboxymethyl cellulose(CMC)interact with each other to form composite vesicles in a wider pH range,especially include the pH range of physiological environment.The force and aggregation behavior of composite vesicles in the process of self-assembly were studied by multiple test methods,and the stability of composite vesicles was investigated.Afterwards,composite vesicles were used to encapsulate nicotinamide(NA).The encapsulation efficiency and sustained release behavior of NA that loaded in composite vesicles were evaluated.The specific research and conclusions are as follows(1)The aggregation behavior of SO/CMC composite assembly was studied by turbidity,surface tension,zeta potential and appearance observation.Turbidity test and appearance observation of the composite solution showed that the turbidity increased with the increase of the mole ratio between SO and CMC(0.02-2)at pH of 6.5,and the appearance of the solution showed a change of colorless transparent-blue opalescence-opalescence.When the molar ratio is from 0.02 to 0.25,the solution is colorless and transparent,and the added value of turbidity is small.When the molar ratio is 0.25-1,the solution appears blue opalescence and the turbidity increases.When the molar ratio is 1-2,the solution appears milky white and the turbidity increases larger.The surface tension and zeta potential experiments showed that with the increase of the molar ratio of SO and CMC,the aggregates of the composite system changed from composite micellar to composite vesicle and to emulsion/free micelles.The morphology and particle size of aggregates were characterized by TEM and DLS to verify the transformation process of aggregates.The interaction between SO and CMC was further confirmed by the analysis of electrical conductivity and infrared spectrum.In the SO/CMC composite system,SO and CMC assemble into different forms of aggregates through the interaction of hydrogen bond and hydrophobicity.Based on the above experimental results,the transformation mechanism of aggregates under acidic conditions was deduced by infrared spectroscopy(2)The pH window of SO/CMC composite vesicles was studied.The size of the pH window was judged by turbidity and apparent phenomenon,and the influence of molar ratio on the pH window of composite vesicles was studied.The results show that when the SO/CMC molar ratio is in the range of 0.4 to 1.6,the pH window of the composite vesicles gradually moves to the acidic direction and widens with the decrease of molar ratio.When the mole ratio of SO and CMC is 1.2 and 1.4,the pH window is 8.0-10.0.When the mole ratio is 1,the pH window is 5.0-8.5;When the mole ratio is 0.6 and 0.8,the pH window is 4.0-8.5.When the mole ratio is 0.4,the pH window of the composite vesicles ranges from 3.5 to 8.5.The morphology and particle size of the composite vesicles were characterized by TEM and DLS to further confirm the formation of the composite vesicles.The formation mechanism of SO/CMC composite vesicles was analyzed by infrared spectroscopy.The results showed that the acting force of SO and CMC self-assembly to form composite vesicles was ion dipole interaction under alkaline conditions,while SO and CMC self-assembly to form composite vesicles through hydrogen bond and hydrophobic interaction under acidic conditions.The effect of wall material concentration on composite vesicles was studied.TEM and DLS test results showed that the particle size of composite vesicles increased gradually with the increase of wall material concentration.The stability of composite vesicles with temperature change(10-60℃)was analyzed by turbidity test.The results showed that the turbidity of composite vesicles with different pH values changed little when the temperature changed,indicating that the composite vesicles had good stability.TEM,DLS and Zeta potential were used to analyze the storage stability of the composite vesicles.The results showed that the composite vesicles could maintain a complete morphology within 90 days,and there was no collapse or aggregation of the composite vesicles.(3)TEM and DLS were used to characterize the morphology and particle size of the composite vesicles enclosing N A at different wall material concentrations.The results showed that the particle size of composite vesicles enclosing NA increased with the increase of wall material concentration,and the composite vesicles also had good morphology,indicating that the morphology of composite vesicles was not affected by drug encapsulation.The results of infrared spectroscopy showed that the absorption peak at 700 cm-1 disappeared and the absorption peak intensity at 1619 cm-1 weakened after the encapsulation of NA in the composite vesicles,indicating that NA was successfully encapsulated in the composite vesicles.By appearance changes and ultraviolet absorption value differences to investigate the stability of NA in composite vesicles.The results showed that with the change of time,the UV absorption peak of free NA changed greatly and the solution also changes color.However,the UV absorption peaks and solution color of the encapsulated NA had little change,indicating that the encapsulated NA could maintain stability in the composite vesicles.The effects of NA concentration and wall material concentration on encapsulation efficiency(EE)and drug loading capacity(DLC)were investigated by ultraviolet spectroscopy.The results showed that with the increase of NA concentration(0.5-1.5mg/mL),EE increased first and then decreased,and the DLC increased first and then remained unchanged.When the concentration of NA is lmg/mL,the maximum of EE is 50.2%and DLC is 21.6%.When the CMC concentration of the wall material component increased from 1.25 to 7.5mM under molar ratio of the wall material component was kept constant at 0.8,the EE of N A firstly increased and then remained unchanged,and the DLC showed a trend of continuous decrease.The release behavior of NA at different temperatures and pH was investigated,the free NA was taken as the control.The results showed that the NA encapsulated in the composite vesicle had a sustained release effect.Finally,zero-order,first-order,Higuchi and Ritger-Peppas models were used to simulate the release of NA under all conditions.The results showed that the Ritger-Peppas correlation coefficient R2 was the highest,so the release of NA was in line with the Ritger-Peppas model,and the release process was controlled by Fickian diffusion. |
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