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Record W3121948094 · doi:10.1002/adtp.202000247

Overcoming the Mucosal Barrier: Tetraether Lipid‐Stabilized Liposomal Nanocarriers Decorated with Cell‐Penetrating Peptides Enable Oral Delivery of Vancomycin

2021· article· en· W3121948094 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueAdvanced Therapeutics · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsNanocarriersBioavailabilityLiposomeDrug deliveryPharmacologyChemistryIn vivoDrugMedicineNanotechnologyMaterials scienceBiochemistryBiology

Abstract

fetched live from OpenAlex

Abstract Despite the high medical need for oral peptide delivery, instability in the gastrointestinal tract and low mucosal permeation still impede this preferred route of administration. Herein, a liposomal nanocarrier combining two self‐reliant strategies to overcome these delivery barriers is reported. This approach enables the design of a nanocarrier system with synergistic properties: tetraether lipids derived from archaea are incorporated into liposomes to provide the particles with the stability required to traverse the stomach. When the surface of the resulting inert particles is modified with cell‐penetrating peptides, mucosal permeation can be achieved. The designed nanocarrier is proven effective by the high mucosal uptake of the glycopeptide antibiotic vancomycin in Ussing chamber studies. Efficacy in vivo is demonstrated in naïve rats, where a highly increased oral bioavailability is obtained for vancomycin, a drug known to be minimally absorbed. In contrast, administration of liposomes with single modification (tetraether lipids) leads to a substantially lower bioavailability. Therapeutic efficacy is proven by the antimicrobial activity of vancomycin in a Galleria mellonella and a systemic infection mouse model. The high oral bioavailability in absence of cytotoxic effects demonstrates that this nanocarrier delivery strategy might boost the oral application of macromolecular drugs in general.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.016
Threshold uncertainty score0.838

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.011
GPT teacher head0.241
Teacher spread0.230 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it