A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
Bibliographic record
Abstract
Noha Khalifa Abo Aasy,1 Doaa Ragab,1,2 Marwa Ahmed Sallam,1,3 Doaa A Abdelmonsif,4,5 Rania G Aly,6 Kadria A Elkhodairy1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; 2Department of Chemical and Biochemical Engineering, Faculty of Engineering, University of Western Ontario, London, Ontario, Canada; 3John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; 4Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Molecular Biology and Nanomedicine Labs, Centre of Excellence for Regenerative Medicine Research & Applications, University of Alexandria, Alexandria, Egypt; 6Department of Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Noha Khalifa Abo AasyDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, 1-Azarita Square, Alexandria, EgyptTel +20 122 710 1058Fax +20 3 487 3273Email drnohakhalifa@yahoo.comIntroduction: This study was conducted to elucidate the chemopreventive potential, cytotoxic, and suppression of cellular metastatic activity of etodolac (ETD)-loaded nanocarriers.Methods: To esteem the effect of charge and composition of the nanovectors on their performance, four types of vectors namely, negative lipid nanovesicles; phosalosomes (N-Phsoms), positive phosalosomes (P-Phsoms), nanostructured lipid carriers (NLCs) and polymeric alginate polymer (AlgNPs) were prepared and compared. ETD was used as a model cyclo-oxygenase-2 (COX-2) inhibitor to evaluate the potency of these nanovectors to increase ETD permeation and retention through human skin and cytotoxicity against squamous cell carcinoma cell line (SCC). Moreover, the chemopreventive activity of ETD nanovector on mice skin cancer model was evaluated.Results: Among the utilized nanovectors, ETD-loaded N-Phsoms depicted spherical vesicles with the smallest particle size (202.96±2.37 nm) and a high zeta potential of −24.8±4.16 mV. N-Phsoms exhibited 1.5, and 3.6 folds increase in the ETD amount deposited in stratum corneum, epidermis and dermis. Moreover, cytotoxicity studies revealed a significant cytotoxic potential of such nanovector with IC50=181.76 compared to free ETD (IC50=982.75), correlated to enhanced cellular internalization. Its efficacy extended to a reduction in the relative tumor weight with 1.70 and 1.51-fold compared to positive control and free ETD, that manifested by a 1.72-fold reduction in both COX-2 and proliferating cell nuclear antigen mRNA (PCNA-mRNA) levels and 2.63-fold elevation in caspase-3 level in skin tumors relative to the positive control group with no hepato-and nephrotoxicity.Conclusion: Encapsulation of ETD in nanovector enhances its in-vitro and in-vivo anti-tumor activity and opens the door for encapsulation of more relevant drugs.Keywords: COX-2, confocal laser microscopy, skin cancer, metastasis, cytotoxicity, chemoprevention
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".