Stimuli-Responsive Self-Crosslinked Ufasomes Of Conjugated Linoleic Acid

Stimuli-responsive vesicles attract much attention due to the stimulation of cell membrane selectivity and the potential applications in intelligent materials, among them, polymer vesicles are most studied. However the applications of polymer vesicles are limited to some extent owing to the complex conditions for synthesis which usually involve organic solvent and cause safety problems. The stimuli-responsive behaviors of micromolecule vesicles are rarely reported because of their poor structural stability. Fatty acid vesicles are a new type of micromolecule vesicles with the most promising development on account of their rich raw material sources, simple preparation process and good ability to embed and sustainable release drug. However, the stimuli-responsive behaviors of fatty acid vesicles are still not studied. In order to solve these problems, the p H and temperature stimuli-responsive behaviors of self-crosslinked vesicles which have been obtained by predecessors in our laboratory were investigated, furthermore, their performances acting as drug deliveries were evaluated. This dissertation mainly focuses on the follwings:(1) Conjugated linoleic acid(CLA) was synthesized from safflower oil through urea inclusion and alkali isomerization. SCLA ufasomes could be prepared by chemical tethering the CLA ufasomes(conjugated linoleic acid ufasomes) which were self-assembled in p H 8.6 at the concentration of 3 mmol?L-1 initiated by moderated UV irradiation. The crosslinking degree of SCLA ufasomes was confirmed by ultraviolet spectrophotometer,and the SCLA ufasomes morphology was characterizated by dynamic laser light scattering(DLS) and transmission electron microscopy(TEM). The experimental results indicated that a relationship existed between the crosslinking degree of SCLA ufasomes and UV irradiation time, moreover, UV irradiation is a kind of mild polymerization method, which would not cause morphology great change of the CLA ufasomes before and after self-crosslinking.(2) p H-responsive morphology evolutions of the SCLA ufasomes were measured by DLS and TEM. The results demonstrated that p H would cause morphology change of SCLA ufasomes, the lower the p H, the bigger the volume and the wall thickness of SCLA ufasomes; the lower the crosslinking degree of SCLA ufasomes, the greater the morphology changing.(3) Temperature-responsive size and morphology evolutions of the SCLA ufasomes were traced by DLS and cryo-transmission electron microscope. It was found that not only the vesicular structure of the SCLA ufasomes was stable but also the vesicular volume was expansive hugely with the increase of temperature from 25 oC to 50 oC, and these changes between 25 oC and 50 oC were reversible. As the temperature increased, both the size and the wall thickness of SCLA ufasomes increased. Furthermore, SCLA ufasomes with different crosslinking degree possessed different levels of temperature-responsive expansion, that was, with the increase of crosslinking degree, the effect of temperature on the volume and the wall thickness of SCLA ufasomes became small.(4) Investigating the in vitro release behavior of anti-cancer drug 5-fluorouracil(5-FU) which was loaded by SCLA ufasomes via dynamic dialysis method. The results showed that these SCLA ufasomes could efficiently encapsulate model substrate 5-FU, more importantly, the 5-FU loaded SCLA ufasomes presented p H- and temperature-responsive 5-FU release behaviors. A rapid release of encapsulated 5-FU could be observed by adjusting the solution p H to acidic or lowering the system temperature. Also, the in vitro release rule of 5-FU conformed to stimuli-responsive mechanism of SCLA ufasomes. All the results revealed that SCLA ufasomes were a kind of potential and intelligent drug carriers.This paper studied on the p H- and temperature- stimuli-responsive behaviors of micromolecule vesicles based on CLA was likely to make up the research blank of fatty acid vesicles and overcome the inherent defects of polymer vesicles. Evaluating the in vitro release drug behaviors of dual p H- and temperature-responsive SCLA ufasomes had a guiding significance to broaden their potential applications in the field of pharmaceutical.