Studies On The Monocaprate Solid Lipid Nanoparticles As Drug Delivery System

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are potential drug delivery systems based on solid lipids. SLN were developed as an alternative carrier system, at the beginning of the 1990s, following the development of emulsions, liposome and polymeric nanoparticles. Compared with traditional carriers, SLN are well-tolerated, have high bioavailability, a nice targeting effect and are amenable to large scale production. However, due to the high crystallization of the solid lipids or blends of solid lipids, drugs tend to be released from the nanoparticles, thus leading to drug expulsion and low loading capacity. To overcome the limitations of SLN, a new generation of lipid nanoparticles, nanostructured lipid carriers (NLC), have been developed in recent years. Although both carrier types are based on solid lipids, SLN consist of pure solid lipids while NLC are made of a solid matrix entrapping liquid oil. It is supposed that the oil incorporation impacted the crystallization state of the solid lipid. With the liquid oil including in the SLN, a less ordered solid lipid matrix is obtained, which leads to more space for the accommodation of guest molecules and increasing the drug pay-load and reducing expulsion of the drug during storage.In the present dissertation, aqueous dispersions of SLN and NLC were successfully prepared by an oil-in-water microemulsion technique using monocaprate (MC) as the solid lipid, medium chain triglyceride (MCT) as the liquid oil and polyethylene glycol sorbitan monooleate (Tween 80) as the emulsifier. The present work aimed to modify the inner structure of an SLN by inducing liquid oil into the system to form an NLC, and then to investigate these new carriers in detail. Several methods including dynamic light scattering (DLS), environmental scanning electron microscopy (ESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier-transform infrared (FTIR) spectra were applied to characterize the particle size, morphology and structure of the NLC and SLN. Furthermore, we incorporated chloramphenicol, the lipophilic drug, into the nanoparticles, and detected the vitro release behavior from SLN and NLC.The microemulsion is formed spontaneously. It is clarity and thermodynamic stability. Preparation SLN and NLC by microemulsion techenique need no special instruments and is easy to operate. In the dissertation, a series of pseudo-ternary phase diagrams based on the nonionic surfactant Tween20/80 were constructed. There were large areas of microemulsion in the phase diagrams. The effect of the liquid oil MCT on the microemulsion area was studied. The results real that there is unconspicuous change of the microemulsion area while a larger biphase area in the corresponding system along with the increasing proportion of MCT. The chloramphenicol loaded leads to some larger microemulsion area. An investigation of the structural transition in the one-phase microemulsion region was carried out by electrical conductivity measurements. The addition of chloramghenicol enables the electrical conductivity of the microemulsion to increase a little.Based on pseudo-ternary phase diagrams, some points were chosen from the microemulsion region and calculated the proportion of each composition. The physical chemistry properties of the particles were studied in details. DLS data show that the average diameters of the SLN and NLC in the nanometer range. Sizes of the particles show a relatively uniformity distribution and the zeta potential is about -12 mV. Factors which affect the sizes of the particles, such as the concentration of the surfactant and the lipid, were studied. The results reveal that sizes of the particles decrease with the increase concentration of the surfactant and MCT. Using ESEM and TEM, SLN and NLC are observed to be nearly spherical particles.X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier-transform infrared (FTIR) spectra were employed to investigate the structure and crystalline behavior of the lipid matrix. Measurement results reveal that imperfect crystallization occurr in the inner core of the NLC particles.Finally, the lipophilic drug chloramphenicol was incorporated into the lipid matrix. The morphology of the drug loaded nanoparticles, the drug crystal state in the lipid matrix and the drug release were studied. Results show that chloramphenicol in the lipid matrix exists as amorphism state. Due to the incorporation of the liquid oil MCT, the accumulative drug release of the NLC is higher than SLN.