Nanotechnology, the branch of technology that is conducted at the atomic, molecular, or supramolecular scale (or ‘nanoscale’) has captured the public imagination since the concept was first introduced over fifty years ago. Even before the relevant technology caught up and allowed nanotechnology to transition from the abstract to the practical realm, it was a subject that inspired scientists and technologists – as well as doomsday enthusiasts and science-fiction writers. With good reason – it is easy to imagine how harnessing the ability to manipulate matter at absurdly small dimensions could open the door for a litany of potential applications in medicine, electronics, energy production and consumer products. And, as just one recent paper has shown (dx.doi.org/10.1016/j.jconrel.2015.12.022), nanotechnology even has a role to play in enhancing drug delivery.
In this paper, the authors have set out to combat the issue of poor drug solubility, which leads to low bioavailability and therapeutic efficacy and can be a great hindrance to the development of otherwise promising compounds. This has particular relevance for medications that target tumour cells, which are often hydrocarbons that are inherently hydrophobic and so require higher dosages to enter aqueous environments. While there have been relatively successful attempts to improve the solubility of pharmaceuticals by ‘nanosizing’ drug formulations to the 10-1000nm range, it is difficult to prevent them aggregating and consequently losing some potency.
To solve this problem, the authors have sought to stabilise drug compounds by using branched copolymer nanoparticles (BCN) made from biocompatible polymers – in this case polyethylene glycol and isopropylacrylamide (PEG-PNIPAM). They synthesised these polymers as branched spheres with varying degrees of cross-linking between the carbon chains, resulting in a structure with both hydrophobic and hydrophilic elements. These characteristics then make it possible to create an emulsion between the drug compound and PEG-PNIPAM when they are mixed together, and subsequent freeze-drying of the emulsion spurred formulation of the organic nanoparticles directly within the pores of the PEG-PNIPAM polymer. Unlike earlier nanosized drugs, these nanoparticles are protected from aggregation within the unique, highly interconnected scaffold structure, which was exquisitely visualised using scanning electron microscopy and well characterised using dynamic light scattering.
The emulsion-freeze-drying process was then applied to the poorly water-soluble drug indomethacine (IMC) to highlight the versatility of this technique. IMC was dissolved in o-xylene and was emulsified with PEG-PNIPAM prior to freeze-drying, which fragmentised the emulsion into nanoparticles. The researchers then showed that the IMC nanoparticles could be readily dissolved in water to form an aqueous dispersion, even after eight months of storage. Not only this, but when the procedure was repeated with two more drugs – ketoprofen and ibuprofen – the resulting nanoparticles achieved an impressive 100% yield. Such a simple and elegant approach could realistically be applied to a wide range of pharmaceuticals to improve drug solubility issues and carve the way for new nanotechnology roles in medical treatment.
Blog written by Chloe Koulouris