| Nonanoic acid is a kind of medium chain saturated fatty acid widely existing in animals and plants.It has light fat and coconut aroma,it is mainly used in the preparation of coconut and berry flavors.Nonanoic acid is cheap and easily available,and is a common raw material for organic synthesis.At present,the research on nonanoic acid mainly focuses on its application as a plant growth regulator to stimulate seed germination and seedling growth and as a herbicide.Fatty acid vesicles have a hollow shell structure,which can be used as carriers to embed drugs in the field of medicine and have potential application value.There are few researches on the preparation of vesicles of medium-chain saturated fatty acids,and there are no reports on their application.In view of this,this paper uses nonanoic acid,a medium-chain saturated fatty acid,as a raw material to self-assemble vesicles,and then studies the migration and expansion of the p H window of vesicles and the embedding/sustained release effects of vesicles on five heterocyclic drugs.In addition,the inclusion compound of corn starch-nonanoic acid was also prepared,and its preparation process and adsorption were preliminarily explored.The research can provide new ideas for the application of nonanoic acid in food,medicine and materials.The main research content is divided into four parts:The first part is about the study of self-assembly of nonanoic acid to form vesicles.Three kinds of saturated fatty acids(caproic acid,nonanoic acid and stearic acid)with different chain lengths were used as raw materials,fatty acids were mixed with salt solution,p H range was adjusted to prepare vesicles,and self-assembly conditions and results were compared.Firstly,the surface tension was measured by the maximum bubble pressure method to obtain the critical micelle concentration offatty acid solution.Preparing a fatty acid salt solution with a concentration 10 times of the critical micelle concentration,and adjusting the p H value to 13 for acid-base titration.The p H window range of vesicles formed by fatty acid self-assembly is determined by an acid-base titration curve method,combination of dynamic light(DLS)and transmission electron microscope(TEM)characterization results further proved the formation of vesicles.The experimental results show that the self-assembly conditions and results of three saturated fatty acids with different chain lengths are quite different.The concentration required for self-assembly of caproic acid solution is relatively high,acid-base titration jumps directly from p H 10.8 to 5.5,and p H titration jumps greatly.After the jump point,the whole solution with p H 1.8 ?5.5 appeared with floccules,and the state did not change much.It was speculated that caproic acid vesicles did not form in this range.The concentration of nonanoic acid solution is half of hexanoic acid.In the range of p H 6.6 ? 7.5,the solution changes from clear to strong milky light.It is speculated that the formation of nonanoic acid vesicles is in this range;The concentration of stearic acid solution to form vesicles is the smallest.When the p H is 8.6 ? 9.4,the appearance of the solution also shows strong milky light.It is speculated that stearic acid vesicles also form in this range.At this time,the number of carboxylate ions and carboxylic acid molecules in the solution is similar.Continue to add hydrochloric acid to the solution,the vesicle disintegrates,the solution appears a lot of turbidity or separation phenomenon.The results of TEM and DLS showed that caproic acid did not form vesicles,but obtained a large number of irregular structures;The vesicles were formed by nonanoic acid,and 63 nm spherical vesicles were obtained at p H = 6.7;the vesicles were also formed by stearic acid,and 72 nm regular vesicles were obtained at p H = 9.0.Both nonanoic acid and stearic acid can form vesicles,but the morphology of nonanoic acid vesicles is regular and the distribution is relatively uniform,and the p H range of the formation is within the applicable p H range of human body,which has not been reported,therefore,we choose medium chain nonanoic acid to continue to explore the application of vesicles.In the second part,the migration and expansion of p H window of nonanoate vesicles were studied.Because of the strong p H stimulation response of nonanoate vesicles,the p H window is narrow,which is not conducive to its application in drug release.In order to widen the p H window of nonanoic acid vesicles,three kinds of surfactants were selected and added to nonanoic acid to form compound vesicles.The migration and expansion of compound vesicles were studied by SI-p H regression curve method.The results showed that the p H window of the vesicles moved and expanded with the addition of three surfactants.When Tween-80 was added,the p H window moved to weak acid direction,and the p H window expanded from 6.6 ? 7.5to 5.5 ? 7.5;When SDS was added,the overall migration and expansion of the p H window of the composite vesicle system was small,and the range of p H window was about 6.2 ? 7.7,the response to p H stimulation was still very high;after the amphoteric surfactant lauramide propyl betaine was added,the p H window moved to the acidic direction.The p H window range of the compound vesicle system was about4.5 ? 6.8,and the overall migration and expansion range was the largest.Tween-80 and SDS can make the p H window of vesicles fall within the range of human life,but the complex vesicles of nonanoate SDS are sensitive to p H stimulation,which is not conducive to the study of drug release.In contrast,Tween-80 compound vesicles have a wider p H range,which can better reduce the p H dependence of vesicles.Tween-80 is a green and safe surfactant that can be used as food without stimulation to human epidermis,it was found by transmission electron microscopy that the composite vesicles of nonanoate Tween-80 could form regular spherical vesicles in the range of5.5 ? 7.5.Therefore,the composite vesicles of nonanoate Tween-80 were selected for further study of drug entrapment / sustained release.In the third part,the entrapment / sustained-release effects of nonanoic acid compound vesicles on five heterocyclic drugs were studied.Five heterocyclic drugs were embedded in nonanoic acid-Tween-80 composite vesicles and placed in an environment simulating human intestinal fluid(p H=6.8).The encapsulation efficiency and slow release effect of nonanoic acid composite vesicles on different drugs weremeasured respectively.The results showed that all the five drugs could be successfully encapsulated,and the entrapment rate was more than 45%,which could be used for further drug release experiments.Comparing the free release results of five heterocyclic drugs with the sustained release results after encapsulation by vesicles,the results show that the compound vesicles of nonanoic acid-tween-80 have sustained release properties after encapsulation of the five drugs,and all can achieve the results of release for 9 ? 10 h in simulated human intestinal fluid environment,and the cumulative release rate is above 35 %,it can fully extend the time for the drug to play its role.Using cheap and easily available nonanoic acid to prepare composite vesicles can save cost,and can also be used as a carrier to wrap drugs and improve the disadvantages of side effects or short acting time caused by direct use of drugs.The research can provide theoretical reference for the application of saturated fatty acids in the field of medicine,and also provide a new idea for the application of nonanoic acid.In the fourth part,the inclusion compound of corn starch nonanoic acid was prepared.The preparation conditions of corn starch nonanoic acid inclusion complex were optimized by star point design response surface method.The inclusion complex was characterized by IR,TG and SEM,and the adsorption test of the inclusion complex was carried out.The results showed that the best preparation conditions of inclusion compound were: the ratio of nonanoic acid to corn starch was 1:10.8(ml: G),the inclusion time was 68 min,and the inclusion temperature was 59.7 ?.The order of the influence of each factor on the inclusion yield was: the ratio of materials > the inclusion temperature > the inclusion time.The process parameters obtained by star point design response surface optimization are reliable and have certain theoretical and practical guiding significance.The results of scanning electron microscopy(SEM)showed that the inclusion complex of corn starch and nonanoic acid had porous characteristics.The results show that the adsorption rate of the inclusion compound to the indicator can reach 67.97 %.The experimental operation is simple and feasible,which provides a theoretical reference for expanding the application of nonanoic acidin adsorption materials. |
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