Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery

• Main Authors: Siti Norain Harun (Author), Haslina Ahmad (Author), Hong Ngee Lim (Author), Suet Lin Chia (Author), Martin R. Gill (Author)
• Format: Book
• Published: MDPI AG, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13020150; 1999-4923
• Keywords: mesoporous silica nanoparticles; ruthenium polypyridyl; drug delivery; IC₅₀; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 2, p 150 (2021)

The ruthenium polypyridyl complex [Ru(dppz)₂PIP]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-C₁₆) as the template. Optimization of the synthesis conditions by Box-Behnken design (BBD) generated MSNs with high surface area response at 833.9 m²g⁻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 (IC₅₀) 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.