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Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of l-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2. [ABSTRACT FROM AUTHOR]

Tantalum arsenide is experimentally verified as a Weyl semimetal recently. However, it is difficult to grow large TaAs single crystals due to the decomposition prior to reaching its melting point. Here we report an improved chemical vapor transport method using iodine as an agent to get large-size, high-quality TaAs single crystals up to 1 cm. X-ray diffraction confirmed that they are tetragonal TaAs. Specific heat of TaAs was measured from 2 K to room temperature, and hence the entropy and enthalpy were obtained, which are helpful in designing the optimal growth conditions. The as-grown crystals exhibit polyhedral morphology consisting of {101}, {001}, {103}, and {112} facets. The key points in crystal growth include using tantalum in the form of foils instead of powder as the starting material, tilting ampule to enhance convections and controlling the concentration of agent iodine. These measures should be applicable to the growth of other transition metal arsenides and phosphides. [ABSTRACT FROM AUTHOR]