Journal
PHARMACEUTICS
Volume 13, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics13020150
Keywords
mesoporous silica nanoparticles; ruthenium polypyridyl; drug delivery; IC50
Categories
Funding
- Ministry of Higher Education Malaysia
- Fundamental Research Grant Scheme [FRGS/1/2017/STG01/UPM/02/6(01-01-17-1913FR)]
- Universiti Putra Malaysia, Graduate Putra Grant [GP-IPS/2017/9577600]
Ask authors/readers for more resources
Ru-PIP is a potential anticancer drug that acts by inhibiting DNA replication, and its limited bioavailability can be overcome by using mesoporous silica nanoparticles (MSNs) as a drug delivery agent. Encapsulated Ru-PIP in MSNs exerted significant cytotoxicity on cancer cell lines, indicating the potential of MSNs as an ideal drug delivery agent for sustained release of Ru-PIP by diffusion.
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 (IC50) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 mu M to <10 mu M 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available