Abstract. Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity and unsatisfied in vivo efficacy limit their applications. In this study, to improve their characteristics as gene delivery carriers, polyethylene glycol (PEG, molecular weight 5,000) was conjugated to G5 and G6 PAMAM dendrimers (PEG-PAMAM) at three different molar ratios of 4%, 8%, and 15% (PEG to surface amine per PAMAM dendrimer molecular). Compared with unconjugated PAMAM dendrimers, PEG conjugation significantly decreased the in vitro and in vivo cytotoxicities and hemolysis of G5 and G6 dendrimers, especially at higher PEG molar ratios. Among all of the PEG-PAMAM dendrimers, 8% PEG-conjugated G5 and G6 dendrimers (G5-8% PEG, G6-8% PEG) resulted in the most efficient muscular gene expression when polyplexes were injected intramuscularly to the quadriceps of neonatal mice. Consistent with the in vivo results, these two 8% PEG-conjugated PAMAM dendrimers could also mediate the highest in vitro transfection in 293A cells. Therefore, G5-8% PEG and G6-8% PEG possess a great potential for gene delivery both in vivo and in vitro.

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Background:Mesaconitine is the main active component of genus aconitum plants that are widely used in clinics in China. However, little has been known about the metabolic pathway of mesaconitine.Objective:To explore the metabolites and propose the pathway of mesaconitine.Materials and Methods:In the present study, mesaconitine (4 mg kg−1) was orally administered to male rats. Then, blood samples collected were pretreated using solid-phase extraction technique with C18 cartridges, and analyzed using LC/MS/MS method with electrospray ionization. Both positive ion mode and collision induced dissociation (CID) were used to elucidate the structures of the major metabolites of mesaconitine.Results:Ten compounds were identified, among which seven were new metabolites, and the metabolic pathway was proposed. The protonated molecular ions of seven new metabolites were at m/z 648, 618, 616, 602, 572, 468, and 542, multistage fragment ions with neutral loss of 28 u (CO), 60 u (CH3COOH), 18 u (H2O), and 32 u (CH3OH). These new metabolites detected firstly in vivo, were named 10-hydroxyl-mesaconitine, hypaconitine, dehydrated mesaconitine 16-O-demethylmesaconitine, 16-O-demethylhypaconitine, and 16-O-demethyl-dehydrated hypaconitine, respectively. Furthermore, the breaking sequence of methoxyl was obtained using quantum chemistry.Conclusion:The study proved that the method of solid-phase extraction technique coupled with MS and quantum chemistry can be applied to the analysis of metabolites in plasma quickly and conveniently.

A Rapid Synthesis of 2-Aryl-Polyhydroxylated Pyrrolidines. -Nitrones (I), (XI) and (XV) undergo Friedel-Crafts-type reaction with electron-rich aromatic compounds in the presence of HCl, generated in situ, to produce the corresponding iminosugar with generally high diastereoselectivity. A decrease is observed in the case of pyrrole and thiophene. Optimized catalytic hydrogenations allow debenzylation/dehydroxylation without any side reaction. -(SU, J.-K.; JIA, Y.-M.; HE, R.; RUI, P.-X.; HAN, N.; HE, X.; XIANG, J.; CHEN, X.; ZHU, J.; YU*, C

Nitrones (I), (XI) and (XV) undergo Friedel—Crafts‐type reaction with electron‐rich aromatic compounds in the presence of HCl, generated in situ, to produce the corresponding iminosugar with generally high diastereoselectivity.