Nanotechnology is widely described as “The understanding and control of matter at dimensions between approximately 1 and 100 nanometers (nm), where unique phenomena enable novel applications not feasible when working with bulk materials or even with single atoms or molecules”(1).
The concept of nanomedicine arose from merging nanoscience and nanotechnology with medicine. Pharmaceutical scientists quickly adopted nanoscience terminology, therefore creating the term ‘nanopharmaceuticals’. Defined specifically as “Pharmaceuticals engineered on the nanoscale i.e. pharmaceuticals where the nanomaterial plays the pivotal therapeutic role or adds additional functionality to the previous compound” (2).
(2) Rivera Gil P, Hühn D, del Mercato LL, Sasse D, Parak WJ. Nanopharmacy: Inorganic nanoscale devices as vectors and active compounds. Pharmacol Res. 2010; 62(2):115–125
NANOFACTURING’s core technology relates to glycan-coated gold nanoparticles. Gold nanoparticles comprise a core of gold metal atoms surrounded by a layer of glycans (sugars) to which various ligands can be attached.
The small size of gold nanoparticles creates several critical qualities for drugs based on this technology:
i) they are able to pass through the normal pore sizes of blood vessels and circulate via interstitial flow to normal and diseased organs, therefore allowing delivery to a large number of disease sites
ii) they are quickly cleared from the body by excretion in the urine without the need for metabolism thereby increasing the elimination of the product.
Gold nanoparticles exhibit a combination of properties unique from other medical nanotechnologies and can provide a multi-functional platform with which to selectively deliver therapeutic agents. Gold nanoparticles can be used to deliver drugs that otherwise exhibit low solubility and poor pharmacokinetics.
There are a number of stages in the nanopharmaceutical manufacturing process, each of which presents its own individual challenges. These issues are amplified when attempting to scale up the manufacture of product, to meet the volume requirements of a marketed drug. Previously, this created a bottleneck in the development, and as a result, delivery of innovative nanopharmaceuticals to the market.
NANOFACTURING addresses several fundamental parts of the manufacturing supply chain: the supply of ligands, pilot scale gold nanopharmaceutical batch manufacture, nanopharmaceutical characterisation and industrial scale up.
It addresses the small and medium-scale needs of early phase clinical trials and niche applications in the EU. It also supports later stage products with large potential markets, by developing clinically compliant and sustainable large-scale manufacturing processes, capable of taking these products through to commercial manufacture and supply.
The correct ligands were supplied with the quantities required for a variety of different nanomedicines for metabolic, central nervous system, antiviral and oncology applications. This involved:
This involved supplying nanomedicine batches for early clinical trials in programs such as metabolic, central nervous system, antiviral and oncology, such as:
The characterisation of the physicochemical and biological characterisation and behaviour of the Gold Nano Particles was critical to the success of the overall scale up project. This is because at all stages during scale-up, it is essential to measure and control these characteristics to ensure that the product fidelity is maintained.
A full package of physicochemical, biophysicochemical and biological characteristics of the nanopharmaceuticals were developed.
The objective was to develop a new manufacturing process using industrial scale technology capable of supplying kilogram quantities of gold nanoparticles required for Phase III and beyond. A pilot and large scale manufacturing lines for the production of nanopharmaceuticals has now been developed for use in Europe, for: