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A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer

Authors Abo Aasy NK, Ragab D, Sallam MA, Abdelmonsif DA, Aly RG, Elkhodairy KA

Received 13 June 2019

Accepted for publication 18 August 2019

Published 17 September 2019 Volume 2019:14 Pages 7561—7581

DOI https://doi.org/10.2147/IJN.S218905

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


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, Egypt

Correspondence: Noha Khalifa Abo Aasy
Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, 1-Azarita Square, Alexandria, Egypt
Tel +20 122 710 1058
Fax +20 3 487 3273
Email drnohakhalifa@yahoo.com

Introduction: 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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