Study On Solid Lipid Nanoparticles And Nanostructured Lipid Carriers For Iontophoretic Transdermal Delivery

In the recent two decades, transdermal drug delivery systems have acquired much attraction. In order to overcome the barrier of stratum soreum, some new technologies such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and iontophoresis, have been developed. Previous studies, however, showed that the individual application of SLN, NLC and iontophoresis is too limited in the enhancement of drugs delivery. Herein, SLN and NLC combined with iontophoresis as novel transdermal delivery system were investigated to improve transdermal delivery action. The results are as follows:1. Triamcinolone acetonide acetate (TA) loaded SLN and NLC were prepared by high-pressure homogenization and thin-film ultrasonication technology. The effects of pre-emulison temperature, the time of ultrasonication, surfactant, the pressure and cycles of homogenization on the nano-particle size and its polydispersity were investigated. SLN and NLC with low partical size (130nm) and narrow PDI (<0.3) were prepared. The spherical shapes of SLN and NLC were observed via an atomic force microscope. DSC and X-ray diffraction results revealed that the characteristic peaks of TA crystalline were vanished, indicating that TA exists in amorphous state in both SLN and NLC.2. Quantum Dots labelled (QDs-SLN ) and NLC (QDs-NLC) were prepared by thin-film ultrasonication technology and high-pressure homogenization, whose particle sizes ranged from 100 nm to 350 nm and PDI are less than 0.30. The results of TEM showed SLN and NLC had spherical shape without aggregation. A characteristic peak of QDs appeared in the X-ray diffraction patterns of QDs-SLN indicating the nanocrystal of QDs in SLN. Fluorescence spectrum showed that both QDs-SLN and QDs-NLC have a stable fluorescent property.(3) The iontophoretic delivery of QDs-SLN was visualized using fluorescent microscopy. The results revealed that iontophoresis could significantly improve the penetration of SLN. The fluorescence of images indicated that the accumulation and the depth of QDs-SLN reached in skin increased with times. Anodal delivery of QDs-SLN resulted in a higher accumulation of QDs-SLN in skin than those of cathodal delivery. Furthermore, the vertical images of skin showed that fluorescence assemble in follicle and dermis, indicating that follicle and the junctions between the corneocyte clusters provide the pathway for SLN penetration into skin.(4) The iontophoretic transport of QDs-NLC was successfully visualized and quantified by confocal laser scanning microscopy. It was demonstrated that QDs-NLC successful penetrated through SC and arrived at deeper skin layers. The fluorescence intensity at SC was increased in initial and then decreased with the increase of particle size of QDs-NLC, while the fluorescence intensity of the epidermis and dermis was decreased significantly with the increase of the particle size. The fluorescence intensity was quantified with Leica Confocal Software 2.61 and expressed as the mean red value (MRV). As to the dermis, the MRV of iontophoretic delivery of NLC₁ (74.9 nm) are 2.3 and 29.3 times greater than those of NLC₂ (143.6 nm) and NLC₃ (335.8 nm), respectively. The fluorescence intensity of the dermis was increased significantly with the increase of the zeta potential. The MRV of the dermis are 211.13 and 273.83 for iontophoretic transport of NLC₅ (+ 11.92 mV) and NLC₆ (+ 56.85 mV), respectively. Additionally, the anodal delivery of QDs-NLC with a similar zeta potential are remarkably enhanced above that of cathodal delivery.