Recent Advances of D-α-tocopherol Polyethylene Glycol 1000 Succinate Based Stimuli-responsive Nanomedicine for Cancer Treatment

D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of TPGS include P-glycoprotein(P-gp)inhibition,penetration promotion,apoptosis induction via mitochondrial-associated apoptotic pathways,multidrug resistant(MDR)reversion,metastasis inhibition and so on.TPGS-based drug delivery systems which are responding to extermal stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect,through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior.In this review,TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed,including pH-responsive,redox-responsive and multi-responsive systems in various formulations.The achievements,mechanisms and diffcrent characteristics of TPGS-bascd stimuli-responsive drug-delivery systems in tumor therapy were also outlined.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine

Hesperetin,an abundant bioactive component of citrus fruits,is poorly water-soluble,resulting in low oral bioavailability.We developed new formulations to improve the water solubility,antioxidant activity,and oral absorption of hesperetin.Two nano-based formulations were developed,namely hesperetin-TPGS(D-α-tocopheryl polyethylene glycol 1000 succinate)micelles and hesperetin-phosphatidylcholine(PC)complexes.These two formulations were prepared by a simple technique called solvent dispersion,using US Food and Drug Administration(FDA)-approved excipients for drugs.Differential scanning calorimetry(DSC)and dynamic light scattering(DLS)were used to characterize the formulations’physical properties.Cytotoxicity analysis,cellular antioxidant activity assay,and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations.The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility,which increased to 21.5-and 20.7-fold,respectively.The hesperetin-TPGS micelles had a small particle size of 26.19 nm,whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm.In addition,the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold,respectively.Importantly,the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration(Cmax)from 2.64μg/mL to 20.67 and 33.09μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold,respectively.The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin,indicating these formulations’potential applications in drugs and healthcare products.

VE TPGS-Loaded Silk Fibroin / Hydroxybutyl Chitosan Nanofibrous Scaffolds for Skin Care Application

Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene glycol 1000 succinate( VE TPGS) via electrospinning. SEM images show that the average nanofibrous diameter has no significant difference when the content of VE TPGS increases to 4. 0%( SF / HBC). However,the average nanofibrous diameter decreases largely to 200 nm when the VE TPGS content reaches 6. 0%. Furthermore,VE TPGS presents a sustained release behavior from the nanofibrous scaffolds. Cell viability studies of mouse skin fibroblasts( L929) demonstrate that VE TPGS loaded SF / HBC nanofibrous scaffolds present good cellular compatibility.Moreover,the incorporation of VE TPGS could strengthen the ability of SF / HBC nanofibrous scaffolds on protecting the cells against oxidation stress using the Tertbutyl hydroperoxide( t-BHP)-induced oxidative injury model. Therefore,VE TPGS-loaded SF /HBC nanofibrous scaffolds might be potential candidates for personal skin care,wound dressing and skin tissue engineering scaffolds.