Pharmacokinetics of Orally Administered Poly(Ethylene Oxide)-block-Poly(ε-Caprolactone) Micelles of Cyclosporine A in Rats: Comparison with Neoral®
Bibliographic record
Abstract
PURPOSE: The aim of this study was to assess the pharmacokinetics of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) micellar formulation of cyclosporine A (CyA) following oral administration in rats making comparisons with its commercial microemulsion formulation, Neoral®. METHODS: PEO-b-PCL copolymer was synthesized and used to form micelles encapsulating CyA. The release of CyA from Neoral® and PEO-b-PCL as well as PEO-b-PCL degradation were assessed in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Polymeric micellar CyA and Neoral® were administered by oral gavage to healthy Wistar rats. At predetermined intervals, rats (n=5 for each time point) were euthanized, samples of blood and plasma were collected and analyzed for CyA using an LC-MS/MS assay. Blood and plasma pharmacokinetic parameters of CyA in its polymeric micellar formulation were compared to those of Neoral®. RESULTS: Polymeric micelles of CyA showed < 15 and 10% increase in diameter in SGF and SIF, respectively, within 24 h. PEO-b-PCL showed signs of minimal degradation when incubated for > 8 h in SGF, but was stable in SIF. Drug release in both SGF and SIF was comparable between the two formulations except for significantly higher release of CyA in SIF only at 24 h time point from Neoral®. Following oral administration (10 mg/kg), the blood AUC0-∞ and tmax of CyA in the polymeric micellar formulation was comparable to that for Neoral®. However, the Cmax of CyA-loaded PEO-b-PCL micelles was significantly (p < 0.05) higher than that obtained with Neoral® (2.10 ± 0.41 versus 1.40 ± 0.25 µg/mL, respectively). CyA had higher blood-to-plasma concentration ratios in polymeric micelles compared to Neoral®, in vivo. CONCLUSION: Our results show that PEO-b-PCL micelles can serve as stable and good solubilizing carriers for oral delivery of CyA providing similar pharmacokinetic profile to that of Neoral®.
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.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".