A Nanocarrier Approach for Oral Peptide Delivery: Evaluation of Cell‐Penetrating‐Peptide‐Modified Liposomal Formulations in Dogs
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract Oral delivery of peptides is severely limited by their instability and poor absorption in the gastrointestinal tract. In contrast to coadministration strategies using medium‐chain fatty acids, which have recently gained regulatory approval with low oral bioavailabilities ≤ 1% (Rybelsus and Mycapssa), efforts to clinically implement delivery systems based on nanocarriers have not been successful to date. The approved drug‐delivery formulations show fairly accurate correlation between clinical results and nonrodent mammal bioavailability, including Beagle dogs for Rybelsus, indicating that Beagle dogs represent a translationally relevant model. Here, a nanocarrier formulation for the oral administration of peptide therapeutics is reported with systemic targets consisting of liposomes decorated with cyclic cell‐penetrating peptides, which significantly increase oral bioavailability in translationally relevant Beagle dogs. This nanocarrier formulation is optimized using the glycopeptide vancomycin, and results in a considerable oral bioavailability of 3.9%. Further, this nanocarrier system increases the oral bioavailability of the large linear peptide therapeutic exenatide 20‐fold, and consistently achieves effective plasma concentrations in Beagle dogs.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| 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 it