Dissertation
Dissertation > Medicine, health > Pharmacy > Pharmacy > Pharmaceutics

Aggregation Behavior of Catanionic Systems Containing Double-chained Surfactant and Their Applications in Sustained Drug Release

Author LiFeiFei
Tutor ZuoYuXiaï¼›ShaoWei
School Shandong University
Course Pharmacy
Keywords drug double-chained surfactants aggregation behavior catanionic vesicle sustained drug release
CLC R943
Type Master's thesis
Year 2011
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Vesicles are the strutures that self-assemble by amphiphilic molecules (small molecule surfactants, phospholipids and block copolymers, etc.) to form a hollow spherical or ellipsoidal single-layer or multi-layer structure. The structures of vesicles are similar to that of original biological cells, and it is usually used as a simple model of research on biomembrane. Vesicles used as a drug carrier have the following advantages:avoiding drug inactivation, reducing the side effects of drugs, improving immune function and synergying with drugs and improving drug bioavailability and therapeutic index. Compared with micelles, microemulsions as drug carriers, the solubilization of drugs is large. So it has been widely used in drug/gene delivery and controlled release, etc.Liposomes which composed of natural phospholipidshave have been widely studied for drug delivery carrier. However, they are rather difficult to prepare and generally have limited stability and shelf life duration. Double-chained catanionic surfactants can spontaneously form vesicles. Compared with synthetic vesicles, they have the following advantages:easy preparation, high stability, low toxicity compared to single surfactant vesicles, surface charge can be controlled by adjusting the ratio of two surfactants.Based on the advantages of catanionic surfactant vesicles as well as for the study on surfactant mixed system, there is no systematic study of double-chained surfactant mixed system. So a systematic study on aggregation behaviors and physicochemical properties of single-chained/double-chained, double-chained/double-chained catanionic surfactant catanionic mixed system and drug/surfactant catanionic mixed system, and study of the impact of polyelectrolyte on physical and chemical properties of catanionic surfactant vesicles. Content and research methods of paper as follows:1. Preparation and properties of DDAB/SDS catanionic vesiclesIn the present study, double-chained cationic surfactant DDAB and single-chained anionic surfactant SDS were the materials that could spontaneously formed vesicles. The aggregation behaviors of the cationic and anionic (catanionic) surfactant vesicles formed by DDAB/SDS in the absence and presence of negatively charged polyelectrolyte were investigated. The charged vesicular dispersions made of cationic surfactant mixed with negatively charged polyelectrolyte, poly (4-styrenesulfonic acid-co-maleic acid) sodium (PSSAMA), to form complexes. Depending on the polyelectrolyte/vesicle charged ratio, complex flocculation or precipitation occured. Characterization of the catanionic vesicles and the complexes were performed by transmission electron microscope (TEM), dynamic light scattering (DLS), conductivity, turbidity, zeta potential measurements. It was demonstrated that the charge ratio of the polyelectrolyte and the net charge of the catanionic vesicles played an important role in the catanionic surfactant/polyelectrolyte system. The charge ratio of vesicle to polyelectrolyte has a significant impact on the property complex systems. Complexes preparated by the "diffusion" are more stable than the "mixing" complexes.2. Preparation and properties of DDAB/NaDEHP catanionic vesiclesBased on the study of mixed system of single-chained/double-chained DDAB/SDS, this section carryed out the study of double-chained/double-chained catanionic surfactant mixed system. Double-chained cationic surfactant DDAB and anionic surfactant NaDEHP were the materials that could spontaneously formed vesicles. NaDEHP is a double-chained anionic surfactant, which molecular structure is similar to AOT containing phosphate group, its molecular structure is closer to phospholipid molecules relative to AOT. So study NaDEHP aggregation behavior in aqueous solution can help people better understand cell structure. First, the same solution concentration of DDAB and NaDEHP was prepared, and mixed in different proportions by keeping the total concentration constant. That was DDAB/NaDEHP ions mixed system. By the DDAB/NaDEHP vesicle dispersion mixing with the polyelectrolyte, complex formatted. The aggregation behaviors of the cationic and anionic (catanionic) surfactant vesicles formed by DDAB/NaDEHP in the absence and presence of negatively charged polyelectrolyte were investigated. The charged vesicular dispersions made of cationic surfactant mixed with negatively charged polyelectrolyte PSSAMA, to form complexes. Depending on the polyelectrolyte/vesicle charged ratio, complex flocculation or precipitation occured. Characterization of the catanionic vesicles and the complexes were performed by TEM, Cryo-TEM, DLS, conductivity, turbidity, zeta potential, isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS) measurements. It was demonstrated that the charge ratio of the polyelectrolyte and the net charge of the catanionic vesicles played an important role in the catanionic surfactant/polyelectrolyte system.3. Properties of catanionic TH/AOT vesicles and their application in sustained drug releaseBy the research on catanionic surfactant mixed system, this paper further carried out the research on aggregation behavior of the charged drug/urfactant catanionic mixed system and the application of drug delivery in the exploratory work. The aggregation behavior of the cationic drug/anionic surfactant vesicles formed by tetracaine hydrochloride (TH) and double-chain surfactant, sodium bis (2-ethylhexyl) sulfosuccinate (AOT), was investigated. To characterize the cationic drug/anionic surfactant system, TEM, DLS, ITC, conductivity, turbidity and zeta potential measurements were performed. By adding TH, a transition from catanionic vesicles to micelles was observed. Furthermore, the drug release behavior of the catanionic aggregates with different drug/AOT molar ratio was studied. The catanionic aggregates exhibited different charge properties, structures, interaction enthalpies and drug release behaviors depending on the composition. The results indicated that the present drug-containing catanionic vesicles had promising applications in drug delivery systems. In this paper a systematic study on aggregation behavior of single-chained/double-chained, double-chained/double-chained catanionic surfactant catanionic mixed system and drug/surfactant catanionic mixed system in aqueous solution enriched the study of catanionic mixed system. The study of amphiphilic drug/surfactant catanionic vesicle established a new drug delivery carriers providing experimental and theoretical basis.

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