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Vitamin C Alimentation via SLC Solute Carriers
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Damian Nydegger, Gergely Gyimesi, Matthias A. Hediger
The SLC23 family consists of four members. Of these, SVCT1 (SLC23A1) and SVCT2 (SLC23A2) are Na+-dependent vitamin C (ascorbic acid) transporters. The third member of the family, SVCT3 (SLC23A3), is an orphan transporter. A fourth member, SLC23A4 (SVCT4 or SNBT1), found in several organisms, exists in humans only as a pseudogene [2]. SVCT1, SVCT2, and SVCT3 sequences were previously identified as yolk sac permease-like proteins, YSPL3, YSPL2, and YSPL1, respectively [9,10], but were not functionally characterized. The Na+-coupled vitamin C transporter SVCT1 was first identified by functional expression of rat cDNA in Xenopus oocytes in our laboratory. The gene encoding SVCT2, SLC23A2, was identified by homologue screening of a rat brain cDNA library [6]. Several groups further cloned and characterized SVCT1 and SVCT2 from different species [2,6,11,12]. SVCT3 is an orphan transporter, since its transport substrates and physiological roles are still unknown [2].
Ascorbate-conjugated nanoparticles for promoted oral delivery of therapeutic drugs via sodium-dependent vitamin C transporter 1 (SVCT1)
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Qiuhua Luo, Mingyan Jiang, Longfa Kou, Ling Zhang, Guyue Li, Qing Yao, Lei Shang, Ying Chen
The current work is to elucidate the potential utility of this strategy to enhance oral bioavailability of therapeutic drug paclitaxel (PTX). Sodium-dependent vitamin C transporter 1 (SVCT1 and SLC23A1) was chosen as a target, which is proposed to handle the bulk transport of apical ascorbic acids from the intestinal tract (Figure 1). It is worth mentioning that SVCT1 expresses throughout the whole intestinal tract, providing a long oral absorption window [23]. Better yet, it belongs to the synergistic transporter system so as to mediate the transport of ascorbic acid with high capability [24]. Based on the above, ascorbate-conjugated nanoparticles (As-PLGA NPs) were designed to target the intestinal SVCT1, with an expectation that such interactions will lead to greater cellular uptake and more efficient intestinal delivery of nanoparticles. The resulting As-PLGA NPs were characterized by particle size distribution, morphology, encapsulation efficiency, in vitro release behaviour and stability. In addition, uptake study and endocytosis pathways of NPs on Caco-2 cell monolayer were performed to clarify the relevant mechanisms on cellular level. The transport mechanisms were also explored by competing inhibition test and Na+-dependent study to confirm the pivotal role of SVCT1 during the uptake process. Finally, the intestinal absorption study as well as biodistribution of As-PLGA NPs were performed by in situ perfusion method and observed by laser confocal study.