Characterization of the Self Assembly of Methoxy Poly(Ethylene Oxide)-block-Poly(α-Benzyl Carboxylate-ε-Caprolactone) for the Solubilization and In Vivo Delivery of Valspodar
Why this work is in the frame
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Bibliographic record
Abstract
The aim of this study was to characterize the nanostructures formed from assembly of poly(ethylene oxide)-bpoly( α-benzyl carboxylate ε-caprolactone) (PEO-b-PBCL) in water, determine the effect of weight fraction of the hydrophilic block( fEO) on their morphology, and to investigate their potential for solubilization and delivery of P-glycoprotein (P-gp) inhibitor, valspodar. Three PEO-b-PBCL block copolymers having fEO ranging from 0.18-0.40 were synthesized. Assembly of PEO-b-PBCL was triggered through a co-solvent evaporation method. The average critical aggregation concentration (CAC) for PEO114-b-PBCL₃₀, PEO₁₁₄-b-PBCL₆₀, and PEO₁₁₄-b-PBCL₉₅ was found to be 62, 41, and 23 nM, respectively. A lower rigidity of the hydrophobic domain in nanostructures formed from the assembly of PEO₁₁₄-b- PBCL₆₀ and PEO₁₁₄-b-PBCL₉₅ in comparison to PEO₁₁₄-b-PBCL₃₀ was observed. The morphology of the assembled structures was characterized by transmission electron microscopy (TEM). The TEM images of PEO₁₁₄-b-PBCL₃₀ (fEO = 0.40) showed the formation of spherical micelles with high polydispersity, whereas the assembly of PEO₁₁₄-b-PBCL₆₀ (fEO = 0.25) and PEO₁₁₄-b-PBCL95 (fEO = 0.18) resulted in a mixed population of spherical micelles and vesicles. Valspodar achieved high loading in all the three PEO-b-PBCL nanocarriers reaching aqueous solubility of nearly 2 mg/mL. The morphology of PEO-b-PBCL carrier did not seem to influence the pharmacokinetics of the encapsulated valspodar in rats following intravenous administration. In conclusion, the results show a potential for PEO-b-PBCL nanocarriers as efficient solubilizing agents for delivery of valspodar.
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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 | 0.001 | 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 | 0.000 |
| 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