Functionalized Caprolactone-Polyethylene Glycol Based Thermo-Responsive Hydrogels of Silibinin for the Treatment of Malignant Melanoma
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
PURPOSE: Silibinin, is a natural compound, which has shown anticancer activity in various malignancies. In this study, we evaluated the anticancer effects of silibinin in B16-F10 melanoma cells and developed a novel thermoresponsive hydrogel for local delivery of this compound. METHOD: A thermoresponsive hydrogel loaded with silibinin was prepared using triblock copolymers of poly[(α-benzyl carboxylate-e-caprolactone)-co-(α-carboxyl-e-caprolactone)]ran-b-PEG-b-[(α-benzyl carboxylate-e-caprolactone) -co-(α-carboxyl-e-caprolactone)]ran (PCBCL-b-PEG-b-PCBCL), namely PolyGelTM, and compared with a Pluronic F-127 formulation of silibinin. Sol-gel transition temperature of hydrogels was measured by inverse flow method and modulated differential scanning calorimetry (MDSC). Silibinin loading efficiency was measured by HPLC. The MTT and clonogenic assays were used to assess the cytotoxicity and anti-proliferative effects of silibinin on B16-F10 melanoma cells. Flow cytotmetry was used to quantify the induced level of apoptosis and measure the intracellular level of activated STAT3 (pSTAT3) following silibinin treatment in B16.F10 cells. The effects of silibinin on the activation of oncogenic proteins were also evaluated by western blot. RESULTS: Silibinin inhibited cell proliferation (IC50 = 67 µM), provoked cell cycle arrest, induced apoptosis, suppressed key oncogenic pathways (i.e STAT3 and MEK/ERK), and enhanced the cytotoxic effects of doxorubicin in B16-F10 cells. Both PolyGelTM and Pluronic F-127 hydrogels were effective in loading silibinin. A lower drug release pattern within 24h, fitting first- order release kinetics, was observed for the release of silibinin from both gels compared to free drug. PolyGelTM demonstrated enhanced percutaneous absorption of silibinin through increasing mouse skin intracellular lipid fluidity as documented by DSC of skin following PolyGelTM use. Silibinin loaded in PolyGel TM inhibited the growth of B16-F10 cells (IC50 = 30 µM) and effectively suppressed pSTAT3 activity in B16-F10 cells at 10 µM. CONCLUSION: Our results imply a great potential for PolyGel TM formulations of silibinin for local treatment of malignant melanoma. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's content page.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it