Multi-functional nanoparticles improved HIV drug absorption
18 Jan 2016 NUS pharmaceutical scientists showed remarkable improvement in oral absorption of HIV drugs by formulating them with multi-functional polymeric nanoparticles.
According to the World Health Organization (WHO) in 2013, there are still new HIV cases affecting 2.1 million worldwide. Currently, HIV infection can be managed by the use of drug cocktail therapies, and it has become a chronic disease rather than a life-threatening one. However, the anti-HIV drugs have a number of shortcomings, such as difficulty dissolving in water, resulting in poor absorption into our body. To address these limitations, a team led by Prof Gigi CHIU from the Department of Pharmacy in NUS has developed a multi-functional polymeric nanoparticle that could tackle both poor drug solubility and poor drug absorption issues of the anti-HIV drugs.
While the anti-HIV drug, saquinavir, is the first US Federal Drug Administration (FDA)-approved protease inhibitor, it is not soluble in water and displays only 4% bioavailability upon oral administration. Furthermore, saquinavir cannot cross the gut lining readily because of the action of a drug efflux pump that limits its absorption into our body. Using a pH-sensitive polymer to allow site-specific drug release and another polymer to inhibit the drug efflux pump for the synthesis of the multi-functional nanoparticles, Prof Chiu’s team could significantly increase the oral bioavailability of saquinavir by 18-fold. Furthermore, this nanoparticle system has outperformed other formulations of saquinavir, where an increase of 3- to 4-fold in bioavailability has been reported.
It is well known in pharmaceutical research that the attrition rate is very high in the drug development process, partly because of poor solubility and poor absorption of the drug candidates. The multi-functional nanoparticle developed by Prof Chiu’s team could be applied to other drug candidates that suffer similar issues of poor solubility and absorption. As for HIV infection that affects millions of children, this nanoparticle formulation of saquinavir is a liquid preparation that could be further developed for easy administration to children.
This research work was presented at the 25th Singapore Pharmacy Congress in September 2015, where Prof Chiu won the best oral presentation.
The graph shows the remarkable increase in plasma concentration of the drug saquinavir administered orally to mice in various forms, including a suspension of saquinavir (SQV, blue symbols), a suspension of saquinavir in combination with ritonavir (SQV/RV, green symbols), and the nanoparticle form (EL-P85-SQV/RV, red symbols). [Image credit: Longwei Sun and Gigi Chiu]
Sun LW, Chiu GN. “pH-sensitive multifunctional nanoparticulate system for improving the oral bioavailability of the saquinavir mesylate/ritonavir combination.” 25th Singapore Pharmacy Congress Abstract Proceedings (2015) Abstract No. CA012.