| Fatty acid vesicles(FAVs)are hollow bilayer structures formed by self-assembly of fatty acids and their salts through weak interaction in aqueous solution.With the availability,good biodegradability and simple assembly mechanism of fatty acids,they have turned into promising vesicles.which make them play an increasingly significant role in the field of food,drug delivery and sustained-release system,simulation of primitive cell models.However.FAVs are dynamic molecular self-assemblies,which still hampered by physical and chemical factors such as temperature,salt,pH and so on.The pH window of the fatty acid vesicles is very narrow and almost around their pKa.It is very crucial to enlarge the pH window of fatty acid vesicles and enhance their stability.At present,there are many studies on the addition of compound substances to change the pH window of fatty acid vesicles.Among them,most of them mainly add small molecules while there are few reports on the addition of poly electrolyte.In this thesis,the method of adding polyelectrolyte was selected to prepare composite vesicles by mixing sodium oleate(SO)with hydroxypropyl trimethylammonium chloride chitosan(HTCC)to expand the pH window for the formation of oleic acid(OA)vesicles,then we stuided stability of the composite vesicles.Meanwhile,the mechanism of the formation of composite vesicles was discussed.Finally,the release behavior of compound vesicles under different conditions was investigated with vitamin C as drug model.The specific studies and conclusions are as follows:(1)First,the effects of different factors on preparation of SO/HTCC composite vesicles were investigated(molar ratio,mixing method,wall material concentration and solvent).The result showed that composite vesicles could form spontaneously when the molar ratio was 0.5-0.8(SO/HTCC repeat unit).The size of the composite vesicles prepared by adding the SO solution to the HTCC solution was more uniform than the method of adding the HTCC solution to the SO solution.The size of composite vesicles increased with the increase of wall material concentration.Compared with OA vesicles,composite vesicles could form in higher ethanol volume fraction aqueous solution.Most of OA vesicles disintegrated in an aqueous solution with an ethanol volume fraction of 5%while composite vesicles could still prepare when ethanol volume fraction was 15%in aqueous solution.Composite vesicles disintegrated when the ethanol volume fraction reached 20%.Then the stability of SO/HTCC composite vesicles was studied.The result showed that SO/HTCC composite vesicles could exist stably at pH values of 1-5 and 10-14,which had a certain widening compared to the 8.2-10 pH window of pure oleic acid vesicles,the wall of composite vesicles under alkaline condition was denser than that under acidic condition.Composite vesicles had high salt tolerance under acidic condition.their size would not change significantly due to the addition of salt.Under alkaline condition,the composite vesicles fused due to the addition of salt,the vesicles’ wall beccame thinner simultaneously.A further increase in salt concentration even led to vesicles’disintegration.When the temperature was 5-40℃,the turbidity of the composite vesicles solution hardly changed under acidic and alkaline condition,indicating that they had good stability.When the temperature was 40-70℃,the composite vesicles under acidic condition were damaged due to the destruction of hydrogen bond,the composite vesicles remained stable under alkaline condition.Ultrasonic made the size of composite vesicles more uniform.The composite vesicles under both pH conditions had good resistance to dilution.The composite vesicles under acidic condition had longer time stability than that under alkaline condition The excellent stability of composite vesicles provided the feasibility for their application in cosmetic,pharmaceutical and other fields.(2)The transformation process of the SO/HTCC system was characterized by turbidity,appearance,Zeta potential,surface tension and DLS.The turbidity experiment indicated that the system gone through four stages with the increase of the SO/HTCC molar ratio:firstly the solution was colorless and transparent,then it appeared blue opalescence,afterwards the solution turned turbid and white,finally,it showed a colorless and transparent state,and precipitate appeared at the bottom.Experiments such as surface tension and micropolarity experiment indicated that with the increase of the SO/HTCC molar ratio,mixed micelles formed firstly,then they turned into composite vesicles.At last composite vesicles disintegrated and micelles formed.In order to verify the morphologic transformation process,the changes of microstructure and size of the compound system wre studied by TEM and DLS The molecular interactions between the vesicle walls were investigated by Zeta potential.conductivity and infrared spectroscopy.The result indicated that the OA and HTCC combined via hydrogen bonding,resulting in the formation of amphiphilic molecules,and then self-assembled into vesicles through the hydrophobic effect under acid condition,the SO associated with HTCC into amphiphilic molecules by electrostatic effect and self-assembled into vesicles through the hydrophobic effect under alkaline condition.In view of the giant composite vesicles in TEM images,the formation mechanism of fusion was put forward.(3)The morphology and size of composite vesicles coated with vitamin C were studied by DLS and TEM(in acid condition).The result showed that the particle size of the composite vesicles increased with the increase of the wall material concentration and they maintained good morphology.The effects of vitamin C concentration and wall material concentration on the EE and DLC of composite vesicles were investigated by ultraviolet spectrophotometry.The results indicated that EE showed a trend of increasing and then decreased with the increase of vitamin C concentration,EE presented a trend of increasing first and then tend to unchanged with the increase of wall material concentration;DLC firstly increased and then tended to remain unchanged with the increase of vitamin C concentration,DLC showed a decreasing trend with the increase of wall material concentration.In summary,the system with HTCC of 1.9mM,SO concentration of 1.4mM and vitamin C concentration of lmg/mL was selected for release behavior study(EE was 29.45%,DLC was 22.39%).The release of composite vesicles containing vitamin C under different conditions was investigated.The results showed that the lower the pH of the solution was,the lower the concentration of NaCl in the solution was and the higher the temperature was,the greater release rate and amount of vitamin C had.Finally,we used Zero Order,First Order,Higuchi and Weibull equation to fit all drug release cruves under different conditons.The results showed that the release curves of composite vesicles loading vitamin C were in the best agreement with the Weibull distribution equation under different conditions(pH,NaCl concentration,temperature).Composite vesicles had good ability of embedding and slow release. |
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