OBJECTIVE:To prepare the levofloxacin(LEF)thermosensitive gel for ophthalmic drug delivery,and to study the drug release in vitro.METHODS:Poloxamer407was used as themosensitive material for the LEF eye drop,the best con?centration of poloxamer in prescription was selected according to the temperature of gel,a novel membraneless model was used to study the drug release.RESUTS:The detected concentration of LEF was in the linear range of3～11?g/ml(r=0.9991,n=6),the recovery was99.62%;The best concentration of poloxamer in prescription was18%;Drug release followed zero-order kinetics,and the quantity of drug release was controlled by that of gel dissolution.CONCLUSION:The preparation is simple in method and easy to control in dosage,therefore it shows a promising future in development.

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

Objective To prepare indocyanine green(ICG)-loaded platelet membrane biomimetic liposome(ICG-PLP)for tumor photothermal therapy,and to preliminarily evaluate its in vitro characteristics.Methods ICG-PLP was prepared by an ultrasound method,and its particle size and zeta potential were determined using a laser particle size analyzer.The encapsulation efficiency of ICG-PLP was detected by ultraviolet spectrophotometry.The photothermal properties of ICG-PLP were investigated under 808 nm near-infrared ray irradiation(2 W/cm2),and the retention of platelet membrane proteins was observed by sodium dodecylsulfate-polyacrylamide gel electrophoresis.The uptake of ICG-PLP by mouse macrophage RAW264.7,human non-small cell lung cancer cell A549,mouse melanoma cell B16-F10,and mouse breast cancer cell 4T1 was observed by a laser confocal microscope.Furthermore,the phototoxicity of ICG-PLP was detected by methyl thiazolyl tetrazolium assay,and the safety of ICG-PLP was preliminarily evaluated according to hemolysis rate and cytocompatibility.Besides,the in vivo retention time of ICG,ICG-loaded liposome and ICG-PLP in healthy SD rats was observed after tail vein injection.Results ICG-PLP was successfully prepared and its encapsulation efficiency,particle size,zeta potential,and the polydispersity index were(97.68±0.01)％,(109.77±0.76)nm,(-21.23±0.84)mV,and 0.22±0.01,respectively.ICG-PLP well retained the proteins on platelet membrane and showed good photothermal properties.Platelet membrane enhanced the uptake of biomimetic nanoparticles by tumor cells A549,B16-F10,and 4T1,and reduced the phagocytosis of biomimetic nanoparticles by macrophages.ICG-PLP exhibited a favorable photothermal therapy effect and could kill tumor cells.Additionally,ICG-PLP displayed a good safety.After intravenous administration,ICG-PLP prolonged the in vivo retention time of ICG in healthy SD rats.Conclusion ICG-PLP has been successfully constructed.It has a great potential in targeted drug delivery and tumor photothermal therapy.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.