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Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery
| Content Provider | MDPI |
|---|---|
| Author | Harun, Siti Norain Ahmad, Haslina Lim, Hong Ngee Chia, Suet Lin Gill, Martin R. |
| Copyright Year | 2021 |
| Description | The ruthenium polypyridyl complex [Ru(dppz)_{2}$PIP]^{2+}$ (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 $(Phen-C_{16}$) as the template. Optimization of the synthesis conditions by Box–Behnken design (BBD) generated MSNs with high surface area response at 833.9 $m^{2}g^{−1}$. 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 $(IC_{50}$) 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. |
| Starting Page | 150 |
| e-ISSN | 19994923 |
| DOI | 10.3390/pharmaceutics13020150 |
| Journal | Pharmaceutics |
| Issue Number | 2 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-01-24 |
| Access Restriction | Open |
| Subject Keyword | Pharmaceutics Pharmacology and Pharmacy Mesoporous Silica Nanoparticles Ruthenium Polypyridyl Drug Delivery Ic50 |
| Content Type | Text |
| Resource Type | Article |
