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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| Materyal Türü: | Makale |
| Dil: | English |
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MDPI AG
2021-11-01
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| Seri Bilgileri: | Molecules |
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| Online Erişim: | https://www.mdpi.com/1420-3049/26/22/6990 |
| _version_ | 1827675898857390080 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:13:49Z |
| format | Article |
| id | doaj.art-c5a51a6f157348aa936687e73cf422ef |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:13:49Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c5a51a6f157348aa936687e73cf422ef2023-11-23T00:36:52ZengMDPI AGMolecules1420-30492021-11-012622699010.3390/molecules26226990Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking StudiesHamid Saeed Shah0Usman Nasrullah1Sumera Zaib2Faisal Usman3Ajmal Khan4Umar Farooq Gohar5Jalal Uddin6Imtiaz Khan7Ahmed Al-Harrasi8Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore 54000, PakistanInstitute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, 60596 Frankfurt am Main, GermanyDepartment of Biochemistry, Faculty of Life Sciences, University of Central Punjab, Lahore 54590, PakistanDepartment of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 66000, PakistanNatural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanInstitute of Industrial Biotechnology, Government College University, Lahore 54590, PakistanDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UKNatural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanThe 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.https://www.mdpi.com/1420-3049/26/22/6990withaferin-Ananospongescancer therapeuticsflow cytometrydrug releasecell cycle |
| spellingShingle | 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 Molecules withaferin-A nanosponges cancer therapeutics flow cytometry drug release cell cycle |
| title | 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_short | 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 |
| topic | withaferin-A nanosponges cancer therapeutics flow cytometry drug release cell cycle |
| url | https://www.mdpi.com/1420-3049/26/22/6990 |
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