Scientists in China have unveiled a way to deliver a platinum-based anticancer drug orally. The system, which works by protecting a prodrug from activation until it reaches the cancer cells, could help avoid the drug’s side effects.

Platinum(IV)-based drugs are used to treat a range of cancers, often combined with other drugs. They are only reduced to the active platinum(II) drug once inside a cancer cell. Currently, healthcare workers administer platinum anticancer drugs through intravenous injections, which results in uncontrolled levels of the drug in the body and associated side effects. Administrating these drugs orally, however, would sustain an optimum concentration of the drug whilst boosting patient comfort and compliance. However, a downside is the prodrugs would be vulnerable to premature reduction into the active drug in the gastrointestinal tract.

Yangzhong Liu and co-workers from the University of Science and Technology of China have discovered a new drug delivery system for platinum(IV) drug asplatin that may sidestep the problem. Asplatin combines the common chemotherapeutic drug cisplatin with aspirin, and is significantly cytotoxic towards cancer cells without encountering cisplatin’s toxicity and resistance problems.

The team tethered asplatin to cholesterol and incorporated this molecular combo into the hydrophobic region of PEGylated poly(lactide-co-glycolide) nanoparticles. The hydrophobic area created by the PEG chains on the nanoparticle protects the drug from degrading before it reaches the cancer cells. The carrier also improves the oral pharmacokinetics and cell uptake, and sustains release of the drug. Tests on mice showed the efficacy of orally delivered asplatin using the new carrier is comparable to that of injected cisplatin and considerably better than that of other Pt(IV) prodrugs delivered orally without the PEGylated nanoparticles.

Mohamed El-Tanani, deputy director of the Institute of Cancer Therapeutics at the University of Bradford, UK, says ‘protecting Pt(IV) compounds from systemic reduction with concomitant enhancement of their cell uptake offers a real opportunity to deliver a higher dose of active platinating agent with potential for lower normal tissue toxicity. This study seems to support that with regard to nephrotoxicity, a dose-limiting side effect of the clinically used platinates.’

El-Tanani and Liu both hope this oral delivery system will work for other drugs currently only available through intravenous injection. ‘We are looking forward to further research exploring the co-delivery of platinum drugs with other drugs for more effective cancer therapy,’ says Liu.