Progress in the field of nanomedicine, as with any new exciting technology, and its translation into clinical applications is being hindered by fundamental factors of a. manufacturing scalability b. therapeutic index of compounds, and c. advanced analytics and detailed characterisation. The key that will differentiate Nanofacturing as beyond state-of-the-art lies in the ability to address these obstacles which in turn will accelerate the translation and conversion of research into successful and scalable clinical applications. This is particularly true in oncology where the promise of nanomedicine is obvious, but its impact and potential is yet to be realized. Despite the launch of some blockbuster drugs like Abraxane and Doxil over 10 years ago, translation since then has been lacking. There are several explanations or factors for this, which are addressed by Nanofacturing.
•Therapeutic Index: this is determined by the efficacy versus toxicity of therapies. The GNP technology is designed to alter the biodistribution, pharmacokinetics and targeting of an active payload and improve the therapeutic index i.e. reduce systemic toxicity and increase efficacy of a compound. The underpinning factors of Midatech’s GNP’s in this regard are their:
-Ultra small size (probably the smallest particles in biomedical use) which allows compounds to get to all areas of the body, and be excreted via the kidneys once their payload has been delivered to the disease site
-Multivalency that allows several entities to be bound to the GNP. This results in a unique and adaptable platform that can satisfy several requirements on one nanoparticle. This ability to attach several moieties to the same nanoparticle including therapeutic and targeting ligands (as well as water solubility and charge determining chemistry) is essential to ensure optimal biodistribution and targeting
•Targeting has been an especially elusive goal in nanomedicine, but Midatech believe their GNP technology has the potential to enable significant targeting of tumour cells; solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.
-Manufacturing Scalability: the innovative GNP manufacturing platform is the leading facility of its kind worldwide; and Nanofacturing is rapidly enabling its development and expansion even further. The use of continuous flow processes is showing significant promise as a viable means of scale up at the same time as allowing very precise control of critical process parameters. This is particularly important for Midatech solid core nanoparticles with the requirement for a very fast reduction step and containment of the hydrogen gas produced by this reaction.Although our current development is focussed on the synthesis of Midatech GNPs, continuous processing readily lends itself to a wide variety of chemical reactions, enabling this technology to be adapted to several nanoparticle manufacturing routes.
The GNP characterisation explored in this project is certainly beyond state-of-the-art. For the first time, GNP characterisation has allowed a deeper understanding of both the physicochemical and biological characteristics and key parameters, and, upon injection, their interactions with both physical and biological barriers. Nanofacturing is employing the most advanced state-of the art-techniques available to measure physical and biological parameters, which has resulted in a deeper understanding of what happens to ultra-small GNPs in the body, especially as they relate to dissociation forces – physical and chemical, aggregation, protein corona adsorption, immune interactions such as phagocytic sequestration, and clearance and metabolism via kidney and liver respectively. Armed with this knowledge, Nanofacturing with its leading academic partners researching these parameters, is developing particles that are optimised for these several key criteria, that in turn will allow ‘super optimised’ constructs
In summary, beyond state-of-the-art is definitively being established by Nanofacturing as a result of addressing key obstacles in the progress of nanomedicine especially manufacturing, cost, toxicity, targeting, biodistribution and therapeutic efficacy parameters
