Självaggregering i blandningar av gallsalteroch fosfolipid undersöktes med statiskoch dynamisk ljusspridning vid 21 ̊ C och 37 ̊ C

Detta är en Master-uppsats från Uppsala universitet/Institutionen för farmaci

Sammanfattning: Introduction: Phospholipids amphiphilic structure gives them special properties such as self-aggregation, emulsifying and wetting properties. Among the various structures resulting from the dissolution of phospholipids in water are the liposome, which acts as a drug carrier. They also act as surfactants for wetting by adsorbing on the crystal surface to increase the hydrophilicity of hydrophobic drugs. Surfactants, such as bile salts, have been shown to have a good ability to solubilize and dissolve non-polar lipids. By mixing with bile salts, phospholipids can easily dissolve and form mixed micelles. For the breakdown of fats in the gastrointestinal tract, mixed micelles formed from bile salts and phospholipid play an important role as well as in solubilizing water-insoluble drugs and other drug delivery applications. Aim: Theaim of this project is to study mixtures of the bile salts sodium deoxycholate (NaDC) and sodium cholate (NaC) with the anionic phospholipid DMPG and to determine the mole fraction (composition) in the aggregates at the transition from micelles to bicolts in bile salt / phospholipid mixtures. In addition, we want to determine the average size and structure of the colloidal particles formed in the solutions near the transition. The phospholipid DMPG has a charge and our results will be compared with previous corresponding studies where the zwitterionic phospholipid DMPC was investigated. Methods: The structure and size of micelles and bilayers formed will be determined by Dynamic Light Scattering (DLS) and Static Light Scattering (SLS) and Determination of refractive index increment of NaC and NaDC. Complementary techniques such as surface tension, small angle X-ray scattering (SAXS) and cryo-TEM may be used. Results and Discussion: This study was able to show that aggregates for systems with a molar ratio of 0.05 to 0.20 of both NaC and NaDC at 21 degrees (°C), have an approximate size range between 3 and 10 nm. At 21 ° C the concentration range studied for both NaC and NaDC shows that the particles are larger in size at lower concentrations. Also, increasing the molar ratio of both bile salts, NaC and NaDC in the samples leads to a reduction in the particle size of the system. At 37 °C the system shows a significant increase in the size of the particles for both the bile salts, NaC and NaDC in a size range between 10 and 400 nm. However, at 37 ° C and for both NaC and NaDC in molar ratios of 0.05 and 0.10, the particle size increases with increasing sample concentration but in molar ratios of 0.15 and 0.20, the particle size decreases with increasing sample concentration. At 21 ° C the light scattering experiments for the systems in NaDC and DMPC showed that the size of the micelles decreased with increasing concentrations while the increasing molar ratio led to increased size corresponding to mixed systems of bile salts and DMPG but not at 37 ° C. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge and the altered conical shape of the bile salts as well as spontaneous curvature at a higher temperature. At 21 ° C the light scattering experiments for the systems in NaDC and DMPC showed that the size of the micelles decreased with increasing concentrations while the increasing molar ratio led to increased size corresponding to mixed systems of bile salts and DMPG but not at 37 ° C. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge and the altered conical shape of the bile salts as well as spontaneous curvature at a higher temperature. Conclusion: At 37 °C for NaC and NaDC in molar ratios of 0.05 and 0.10 other cmc are obtained, indicating the presence of large structures in the system. Where these large worm-like or rod-like structures are formed by micelles. Accurate prediction of what structures may be present in the system requires more detailed and more appropriate research methods which in turn also need more time to achieve the result. Due to the project's time constraints, it became impossible to use these methods. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge. The bile salts' end conformation form as well as spontaneous curvature at higher temperatures.

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