Yibin Yu,Shuo Xu,Shihui Yu,Jinyu Li,Guoxin Tan,Sanming Li,Weisan Pan
We developed a hybrid nanostructured lipid carrier/dual pH- and thermo-sensitive hydrogel (NLC-Gel) for ocular delivery of quercetin (QN). The hydrogel consisted of carboxymethyl chitosan and poloxamer 407 (P407) was cross-linked using a naturally occurring cross-linker genipin (GP), while the hydrogel cross-linked using glutaraldehyde was used as a control. NLC loaded with quercetin/hydrogel cross-linked by a genipin hybrid drug delivery system (QN-NLC-Gel-GP) exhibited better cytocompatibility and lower ocular irritation than its glutaraldehyde counterpart. The levels of cellular uptake in NLC and NLC-Gel groups were improved. The results of fluorescence imaging and ex vivo transcorneal study indicated that NLC could facilitate transcorneal penetration of lipophilic molecules and incorporation into the hydrogel could increase the precorneal residence time of NLC. The area under the curve of quercetin in the NLC-Gel group was 4.4-fold that in the Eye drops group because of a longer precorneal retention time. In summary, the developed drug delivery system has enormous potential for ophthalmic applications.
This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 μg/cm 2 ) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 μg/cm 2 ). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases. Graphical Abstract
危险品化学品经营许可证（带存储）