High ceramide content liposomes with in vivo antitumor activity.
Bibliographic record
Abstract
BACKGROUND: The pro-apoptotic activity of ceramide lipids has made this an exciting new target for therapeutic manipulation. While approaches using exogenous application of short-chain ceramides and modulation of endogenous ceramide levels via manipulation of metabolic pathways have been explored, controlled delivery of natural ceramide has not been previously reported. In this paper we describe the formulation of novel liposomes containing high levels of natural ceramide in the lipid bilayer for the purpose of controlled ceramide delivery. MATERIALS AND METHODS: Liposomes were characterized by cryo-transmission electron microscopy, quasi-elastic light scattering and trapped volume analysis. Pharmacokinetic analysis was performed following i.v. bolus dosing, and antitumor activity was evaluated following i.v. bolus and i.p. dosing in the J774 ascites tumor model. RESULTS: Stable ceramide-containing liposomes exhibited pharmacokinetic properties suitable for in vivo applications and resulted in an increase in lifespan of greater than 20% compared to control liposomes following i.v. bolus and i.p. administration. CONCLUSION: This work demonstrates proof-of-concept that delivery of exogenous natural ceramide lipid has antitumor activity in vivo, and highlights the potential utility of ceramide-based liposomes as a novel strategy for cancer chemotherapy based on controlled ceramide delivery.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 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".