hBMSCs possess of great potential to differentiate into functional neurons, indicating that hBMSCs may be an ideal cell source in managing a variety of clinical diseases such as spinal cord injury.

In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG 1000 -HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG 1000 -HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC 50 value against HepG2 cells and 14.1 times lower IC 50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG 1000 -HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy.

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AbstractA pharmacokinetic comparison was made to evaluate the influence from other components in the Radix Puerariae Extract on pharmacokinetic behavior of Puerarin. Samples of blood and brain were collected by microdialysis and determined by high-performance liquid chromatography–mass spectrometry (MS)/MS. Pharmacokinetic parameters were estimated from the concentration versus time data using non-compartmental methods. In addition, a comparative pharmacokinetic study of Puerarin in stroke rats was studied after administration of the Radix Puerariae Extract via different routes to find an effective way to deliver drug into brain. Obvious pharmacokinetic differences were also observed in comparison between the Puerarin group and the Radix Puerariae Extract group based on middle cerebral artery occlusion (MCAO) rats. The Cmax and area under the curve (AUC) of Puerarin in olfactory bulb of the Extract group significantly reduced when it was intravenously administered. However, the AUCs of Puerarin in plasma are 134.72 and 1707.02 mg/L min, via intranasal and intravenous administration of the Radix Puerariae Extract, respectively. The AUC of the intranasal group in brain is seven times higher than that of intravenous administration. Other ingredients in the Extract may affect the disposition of Puerarin and its transportation through the blood–brain barrier via intravenous administration. But intranasal administration is an effective route to deliver isoflavone-C-glycoside with poor hydrophilicity into brain.