Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

[Image: see text] Amphiphilic macrocycles, such as p-sulfonatocalix[6]arenes (p-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity...

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Autores principales: Fahmy, Sherif Ashraf, Issa, Marwa Y., Saleh, Basma M., Meselhy, Meselhy Ragab, Azzazy, Hassan Mohamed El-Said
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153973/
https://www.ncbi.nlm.nih.gov/pubmed/34056350
http://dx.doi.org/10.1021/acsomega.1c00455
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author Fahmy, Sherif Ashraf
Issa, Marwa Y.
Saleh, Basma M.
Meselhy, Meselhy Ragab
Azzazy, Hassan Mohamed El-Said
author_facet Fahmy, Sherif Ashraf
Issa, Marwa Y.
Saleh, Basma M.
Meselhy, Meselhy Ragab
Azzazy, Hassan Mohamed El-Said
author_sort Fahmy, Sherif Ashraf
collection PubMed
description [Image: see text] Amphiphilic macrocycles, such as p-sulfonatocalix[6]arenes (p-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L. seeds. Ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p-SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of −30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC(50) values of HARF encapsulated in p-SC6 (H/p-SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC(50) of the H/p-SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p-SC6 significantly increases its antioxidant and cytotoxic activities.
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spelling pubmed-81539732021-05-27 Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities Fahmy, Sherif Ashraf Issa, Marwa Y. Saleh, Basma M. Meselhy, Meselhy Ragab Azzazy, Hassan Mohamed El-Said ACS Omega [Image: see text] Amphiphilic macrocycles, such as p-sulfonatocalix[6]arenes (p-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L. seeds. Ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p-SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of −30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC(50) values of HARF encapsulated in p-SC6 (H/p-SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC(50) of the H/p-SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p-SC6 significantly increases its antioxidant and cytotoxic activities. American Chemical Society 2021-04-27 /pmc/articles/PMC8153973/ /pubmed/34056350 http://dx.doi.org/10.1021/acsomega.1c00455 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Fahmy, Sherif Ashraf
Issa, Marwa Y.
Saleh, Basma M.
Meselhy, Meselhy Ragab
Azzazy, Hassan Mohamed El-Said
Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title_full Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title_fullStr Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title_full_unstemmed Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title_short Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities
title_sort peganum harmala alkaloids self-assembled supramolecular nanocapsules with enhanced antioxidant and cytotoxic activities
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153973/
https://www.ncbi.nlm.nih.gov/pubmed/34056350
http://dx.doi.org/10.1021/acsomega.1c00455
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