Formulation Development Forum: Nanotechnology-based Drug Delivery

Drug-delivery approaches that better control and target delivery are important to achieve clinical efficacy. Several recent interesting approaches involve gold nanoparticles for targeting tumor sites and elastic capsules using nanosized flakes.

Researchers at the University of Sydney in Australia, led by Nial Wheate, senior lecturer in the Faculty of Pharmacy, and researchers from the University of Strathclyde and the University of Glasgow in Scotland recently reported on delivering the anticancer drug cisplatin using gold-coated iron oxide nanoparticles for enhanced tumor targeting (1). The researchers used this approach to overcome some challenges of cisplatin, namely poor bioavailability, severe dose-limiting side effects, and rapid development of drug resistance (1). The iron oxide core was coated in a protective layer of gold before the anticancer drug cisplatin was attached to the gold coating using spaghetti-like strings of polymer, according to a May 31, University of Sydney press release.

The technology was demonstrated when the team grew cancer cells in plates. When they placed a magnet under the plates, the drug affected and killed only those cells growing near the magnet, leaving the others unharmed, The potential benefit of this targeted drug- delivery method is reduction of side-effects due to the chemotherapeutic drug traveling to other cells.

The iron oxide nanoparticles (FeNPs) were synthesised via a coprecipitation method before gold was reduced onto its surface (Au@FeNPs). Aquated cisplatin was used to attach {Pt(NH₃)₂} to the nanoparticles by a thiolated polyethylene glycol linker forming the desired product (Pt@Au@FeNP). The nanoparticles were characterized by dynamic light scattering, scanning transmission electron microscopy, UV visible spectrophotometry, inductively coupled plasma mass spectrometry, and electron probe microanalysis. Nanoparticle drug loading was found to be 7.9 X 10^-4 moles of platinum per gram of gold. External magnets were used to show that the nanoparticles could be accumulated in specific regions and that cell-growth inhibition was localized to those areas (1).

In another development, researchers at the National Institute for Material Science in Japan recently developed a new elastic capsule using an inorganic nanometer-thickness flake-shaped material (nanosheets). Tests of the new capsule demonstrated that the release duration of anticancer drugs and other drugs can be controlled freely and can also be extended by several times by using the newly developed capsule.

The researchers were seeking to overcome some of the challenges of inorganic and organic materials conventionally used in capsules, according to a May 9, 2012, press release of the National Institute for Material Science in Japan. Inorganic capsules are hard, strong, and durable, but their structures are not easily adjusted to adapt to conditions. Organic capsules are flexible and structural adjustment is possible, but they have the drawback of low mechanical strength. In this research, a soft capsule was developed by creating an assembly of nanosheets of silica, which is an inorganic material. While this capsule consists of a mechanically stable inorganic material, free control of its structure is also possible.

This capsule expands and contracts when heated and cooled, and the size of the pores in the outer wall, which are formed by the spaces between the nanosheets and serve as passages for drug release, can be controlled over a wide range by adjusting pH to various levels, according to the press release. As a result, the sustained-release time of the anticancer drug DOX was successfully extended by several times in comparison with conventional porous capsules having a simple structure. It was also possible to control the drug-release duration and drug-storage amount by changing the pore structure of the capsule, thereby changing the drug-release routes under appropriate pH conditions (2).

References

1. N. Wheate et al., "Cisplatin Drug Delivery Using Gold-Coated Iron Oxide Nanoparticles for Enhanced Tumor Targeting with External Magnetic Fields," Inorg. Chimica Acta, online, DOI10.1016/j.ica.2012.05.012, May 30, 2012.

2. Q. Ji et al.,"Flake-Shell Capsules: Adjustable Inorganic Structures," Small, online, DOI: 10.1002/chin.201223201, May 7, 2012.