Ascorbate-conjugated nanoparticles for promoted oral delivery of therapeutic drugs via sodium-dependent vitamin C transporter 1 (SVCT1)
Bibliographic record
Abstract
Oral administration is the most convenient route for most patients. However, many therapeutics in clinical applications are limited due to the poor solubility and permeability as well as low stability in the intestinal tract. It still remains a significant challenge of how to improve the oral drug bioavailability. In this study, we have designed functional ascorbate-conjugated NPs (As-PLGA NPs) to offer the interaction with sodium-dependent vitamin C transporter 1 (SVCT1) on the epithelial cells. Cellular uptake study indicated that conjugation of 20% ascorbate to the surface of PLGA NPs might achieve a maximum efficacy in Caco-2 cells. Besides, the majority of As-PLGA NPs were predominantly internalized into cells via caveolae-mediated pathway and thereby circumnavigated the lysosomal compartment. Furthermore, the competitive inhibition test and Na+-dependent study provide strong evidence that SVCT1 was involved in the internalization of As-PLGA NPs. Finally, the biodistribution and perfusion study demonstrated that As-PLGA NPs accumulated in the villi and penetrated to the basolateral side, thus significantly enhanced the intestinal absorption. In summary, it showed that SVCT1 expressed in the apical side of epithelial cells might be conceivably exploited as a potential target for oral delivery of therapeutic drug-loaded pharmaceutical nanocarriers.By means of the interaction of SVCT1 and ascorbate on the surface of PLGA NPs, the nanoparticles and transporters accumulated in coated pits, internalizing as ligand-transporter complexes and switched the subcellular sorting of NPs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".