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

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...

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Autores principales:	Abo Aasy NK, Ragab D, Sallam MA, Abdelmonsif DA, Aly RG, Elkhodairy KA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	COX-2 confocal laser microscopy skin cancer metastasis cytotoxicity chemoprevention Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/86b291caac844c6ca14564ac014906ca
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spelling	oai:doaj.org-article:86b291caac844c6ca14564ac014906ca2021-12-02T04:45:09ZA comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer1178-2013https://doaj.org/article/86b291caac844c6ca14564ac014906ca2019-09-01T00:00:00Zhttps://www.dovepress.com/a-comparative-study-the-prospective-influence-of-nanovectors-in-levera-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Noha 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, chemopreventionAbo Aasy NKRagab DSallam MAAbdelmonsif DAAly RGElkhodairy KADove Medical PressarticleCOX-2confocal laser microscopyskin cancermetastasiscytotoxicitychemopreventionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 7561-7581 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	COX-2 confocal laser microscopy skin cancer metastasis cytotoxicity chemoprevention Medicine (General) R5-920
spellingShingle	COX-2 confocal laser microscopy skin cancer metastasis cytotoxicity chemoprevention Medicine (General) R5-920 Abo Aasy NK Ragab D Sallam MA Abdelmonsif DA Aly RG Elkhodairy KA A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
description	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
format	article
author	Abo Aasy NK Ragab D Sallam MA Abdelmonsif DA Aly RG Elkhodairy KA
author_facet	Abo Aasy NK Ragab D Sallam MA Abdelmonsif DA Aly RG Elkhodairy KA
author_sort	Abo Aasy NK
title	A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
title_short	A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
title_full	A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
title_fullStr	A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
title_full_unstemmed	A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer
title_sort	comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of cox-2 inhibitors against skin cancer
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/86b291caac844c6ca14564ac014906ca
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A comparative study: the prospective influence of nanovectors in leveraging the chemopreventive potential of COX-2 inhibitors against skin cancer

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