Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery
The ruthenium polypyridyl complex [Ru(dppz)<sub>2</sub>PIP]<sup>2+</sup> (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP i...
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MDPI AG
2021-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/2/150 |
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| author | Siti Norain Harun Haslina Ahmad Hong Ngee Lim Suet Lin Chia Martin R. Gill |
| author_facet | Siti Norain Harun Haslina Ahmad Hong Ngee Lim Suet Lin Chia Martin R. Gill |
| author_sort | Siti Norain Harun |
| collection | DOAJ |
| description | The ruthenium polypyridyl complex [Ru(dppz)<sub>2</sub>PIP]<sup>2+</sup> (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C<sub>16</sub>) as the template. Optimization of the synthesis conditions by Box–Behnken design (BBD) generated MSNs with high surface area response at 833.9 m<sup>2</sup>g<sup>−1</sup>. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC<sub>50</sub>) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T03:50:41Z |
| publishDate | 2021-01-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-9aae4162b4bf455294d2345071fa84fd2023-12-03T14:28:28ZengMDPI AGPharmaceutics1999-49232021-01-0113215010.3390/pharmaceutics13020150Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug DeliverySiti Norain Harun0Haslina Ahmad1Hong Ngee Lim2Suet Lin Chia3Martin R. Gill4Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, MalaysiaUPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Unversiti Putra Malaysia, Serdang 43400 UPM, Selangor, MalaysiaDepartment of Chemistry, Swansea University, Swansea SA2 8PP, UKThe ruthenium polypyridyl complex [Ru(dppz)<sub>2</sub>PIP]<sup>2+</sup> (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C<sub>16</sub>) as the template. Optimization of the synthesis conditions by Box–Behnken design (BBD) generated MSNs with high surface area response at 833.9 m<sup>2</sup>g<sup>−1</sup>. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC<sub>50</sub>) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period.https://www.mdpi.com/1999-4923/13/2/150mesoporous silica nanoparticlesruthenium polypyridyldrug deliveryIC<sub>50</sub> |
| spellingShingle | Siti Norain Harun Haslina Ahmad Hong Ngee Lim Suet Lin Chia Martin R. Gill Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery Pharmaceutics mesoporous silica nanoparticles ruthenium polypyridyl drug delivery IC<sub>50</sub> |
| title | Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery |
| title_full | Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery |
| title_fullStr | Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery |
| title_full_unstemmed | Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery |
| title_short | Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery |
| title_sort | synthesis and optimization of mesoporous silica nanoparticles for ruthenium polypyridyl drug delivery |
| topic | mesoporous silica nanoparticles ruthenium polypyridyl drug delivery IC<sub>50</sub> |
| url | https://www.mdpi.com/1999-4923/13/2/150 |
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