Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificia...

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Autores principales:	Hamid Saeed Shah, Usman Nasrullah, Sumera Zaib, Faisal Usman, Ajmal Khan, Umar Farooq Gohar, Jalal Uddin, Imtiaz Khan, Ahmed Al-Harrasi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	withaferin-A nanosponges cancer therapeutics flow cytometry drug release cell cycle Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/c5a51a6f157348aa936687e73cf422ef
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spelling	oai:doaj.org-article:c5a51a6f157348aa936687e73cf422ef2021-11-25T18:28:57ZPreparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies10.3390/molecules262269901420-3049https://doaj.org/article/c5a51a6f157348aa936687e73cf422ef2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6990https://doaj.org/toc/1420-3049The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in <i>Withania somnifera</i>, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC<sub>50</sub> = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.Hamid Saeed ShahUsman NasrullahSumera ZaibFaisal UsmanAjmal KhanUmar Farooq GoharJalal UddinImtiaz KhanAhmed Al-HarrasiMDPI AGarticlewithaferin-Ananospongescancer therapeuticsflow cytometrydrug releasecell cycleOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6990, p 6990 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	withaferin-A nanosponges cancer therapeutics flow cytometry drug release cell cycle Organic chemistry QD241-441
spellingShingle	withaferin-A nanosponges cancer therapeutics flow cytometry drug release cell cycle Organic chemistry QD241-441 Hamid Saeed Shah Usman Nasrullah Sumera Zaib Faisal Usman Ajmal Khan Umar Farooq Gohar Jalal Uddin Imtiaz Khan Ahmed Al-Harrasi Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
description	The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in <i>Withania somnifera</i>, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC<sub>50</sub> = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.
format	article
author	Hamid Saeed Shah Usman Nasrullah Sumera Zaib Faisal Usman Ajmal Khan Umar Farooq Gohar Jalal Uddin Imtiaz Khan Ahmed Al-Harrasi
author_facet	Hamid Saeed Shah Usman Nasrullah Sumera Zaib Faisal Usman Ajmal Khan Umar Farooq Gohar Jalal Uddin Imtiaz Khan Ahmed Al-Harrasi
author_sort	Hamid Saeed Shah
title	Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
title_short	Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
title_full	Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
title_fullStr	Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
title_full_unstemmed	Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies
title_sort	preparation, characterization, and pharmacological investigation of withaferin-a loaded nanosponges for cancer therapy; in vitro, in vivo and molecular docking studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c5a51a6f157348aa936687e73cf422ef
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Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies

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