Liposomal Templating,Association with Mammalian Cells,and Cytotoxicity of Poly(vinyl alcohol) Physical Hydrogel Nanoparticles

The assembly, cellular internalization, and cytotoxicity of nanoparticles based on physical hydrogels of poly(vinyl alcohol) (PVA) are reported. PVA nanoparticles are assembled using a liposomal templating technique followed by removal of the lipids using isopropanol, a process that requires the presence of a custom‐made block copolymer, poly(vinyl alcohol‐b‐vinyl pyrrolidone), to avoid aggregation of the nanoparticles. Polymer hydrogelation is induced via incubation in aqueous isopropyl alcohol solution, which results in PVA hydrogel nanoparticles (PVA HNP) with excellent colloidal stability and stability towards disintegration over at least 24 h. Pristine PVA HNP are found to be remarkably stealth‐like and exhibit negligible cellular internalization. This feature is likely inherent with the low fouling nature of PVA and makes PVA HNP attractive for targeted drug delivery with a low level of association with non‐targeted cells and tissues. Blending PVA with varied amounts of collagen results in colloidal hydrogel particles with a well pronounced tendency towards association with mammalian cells, specifically hepatocytes and endothelial cells. The association of PVA HNP elicits minimal changes in cellular proliferation, making these novel hydrogel particles convenient tools for drug delivery applications and creation of implantable artificial organelles and sensors.     

Stereoselective Conversion of Aucubin into Polyfunctionalized Tetrahydro‐1H‐cyclopenta[c]furan Glucosides

Mitsunobu reaction of 2′,3′,4′,6′,10‐penta‐O‐pivaloylaucubin ( 6 ) with phthalimide, triphenylphosphine, and diethyl azodicarboxylate gave (6R)‐6‐phthalimido‐perpivaloylbartsioside ( 10 ) (Scheme 1). Selective oxidation reactions performed with perpivaloylaucubin ( 12 ) yielded (1R)‐ and (1S)‐3(β‐D ‐glucopyranosyloxy)‐1H‐cyclopenta[c]furan‐1‐carboxaldehydes 13 and 14 respectively (Scheme 2). Similarly, perpivaloyl‐6‐epiaucubin ( 9 ) and 10 afforded the corresponding (1S)‐carboxaldehyde 15 and (1R)‐carboxaldehyde 16 , respectively. The protected cyclopentafuran glycosides obtained in this way are versatile synthons, which may prove useful for further chemical diversification.     

Validation of a Reversed-Phase Liquid Chromatographic Method for the Determination of Metronidazole in Transparent Oil-Water-Gel Formulations

A high performance liquid chromatographic (HPLC) method for the determination of metronidazole in new gel formulations was developed and validated according to the recommendations of the International Harmonization Conference. An adaptation of the method described for metronidazole determination in plasma has been used, and the step of extraction has been developed. The method was demonstrated to be linear over a range of 60–140% of nominal label claim, accurate (100.08±0.63%) and precise (0.67% for intra-assay and 1.68% for inter-assay). Single point calibration was chosen for analysis because of its simplicity and wide use in the pharmaceutical industry for content uniformity analysis.     

Recent results on kaon decays by the NA48/2 experiment at CERN

The NA48/2 experiment reports the first observation of the rare decay K^± → π^±π⁰e⁺e^?, based on about 2000 candidates from 2003 data. The preliminary branching ratio in the full kinematic region is \(\mathcal {B}(K^{\pm } \to \pi ^{\pm }\pi ^{0}e^{+}e^{-})=(4.06\pm 0.17)\cdot 10^{-6}\). A sample of 4.687 × 10⁶\(K^{\pm }\to \pi ^{\pm }{\pi ^{0}_{D}}\) events collected in 2003/4 is analyzed to search for the dark photon (\(A^{\prime }\)) via the decay chain K^± → π^±π⁰, \(\pi ^{0}\to \gamma A^{\prime }\), \(A^{\prime }\to e^{+}e^{-}\). No signal is observed, limits in the plane mixing parameter ε² versus its mass \(m_{A^{\prime }}\) are reported.