THE PLATFORM TECHNOLOGY
The short polymer technology was developed by researchers at Deakin University and has been commercialised through HeiQ Pty Ltd (manufacturing processes), and Cytomatrix Ltd. Cytomatrix holds a world-wide exclusive license to the use in non-textile and graphene applications.
Short fibres are routinely manufactured using a process called “electrospinning”. In this process, a polymer solution is injected through a needle towards a plate. A high voltage difference between the tip of the needle and the plate causes the solution to narrow to nanometer dimensions (the “Taylor cone”). As the fibre drops towards the plate, the solvent evaporates, allowing the polymer to gelate and form a fibre. This is then deposited onto the plate as a nanofibre mat.
Limitations of this method include the type of polymer that can be used (must be electrically charged, and soluble in an organic solvent that will evaporate quickly), and the fact that only long, continuous fibres can be created.
Figure 1 Electrospinning process
Short nano and micron sized fibres have a number of desirable properties, including the fact that they will remain in aqueous suspension. This makes chemical modification/functionalisation considerably easier, as well as enabling new applications that require suspension. They can also be used to coat complex surfaces. However, until recently, the only available methods for their manufacture have been tedious and low yield.
In 2012 Cytomatrix patented a new method that has distinct advantages over published approaches. The Cytomatrix method also uses shear forces to stretch and break up the fibres, but in this case the polymer can be dissolved in any solvent (including water). The gelating agent used depends on the polymer, but is generally a solvent in which the polymer is non-soluble (for example, butanol is used for many water soluble polymers). The result is highly efficient production of a wide range of different fibres in a very short time (generally 30 seconds to a minute to produce gram quantities using small scale equipment). Cleaning and purifying the fibres requires simple centrifugation. The ability to use a wide range of solvent/gelation combinations also substantially extends the range of manufacturing options (e.g. mixed polymer fibres).
The mechanism of fibre formation is shown in Figure 2. A stream of polymer solution is injected into a flowing gelation fluid that creates a shear force on the polymer while also gelating it. As a result, the polymer stream forms into a fibre that then breaks up into short segments. The breakup of the fibre is dependent on a number of factors including polymer type and concentration, shear force and temperature.
Figure 2 Mechanism of fibre formation
The Technology Platform
This manufacturing method is extraordinarily versatile and lends itself to applications in many different fields such as textiles, coatings, cosmetics, biomedical, veterinary, agriculture and food science.
Advantages of Short Polymer fibres over electrospun fibres and nanoparticles.
Application to Immunotherapy Vaccines for Cancer Treatment
Cytomatrix has developed methods for incorporation of antigens and dendritic cell (DC) promoting elements into biodegradable SPF that can be administered by simple injection. These SPF have the potential to promote DC differentiation both in the laboratory (in vitro) and in vivo, and to present specific antigens, which are incorporated into the SPF, to these DCs for presentation to T-cells to initiate an immune response. The SPF method is simple and rapid, and all the components needed are available at clinical grade, reducing the regulatory hurdles for clinical development. The method is also highly versatile, enabling a range of different antigens to be incorporated into the SPF, and enabling mixtures of fibre types to be used.
Cytomatrix has successfully demonstrated that our proprietary short-polymer-fibre (SPF) system can incorporate proteins, peptides and oligonucleotides on different polymer backbones. Cytomatrix is building on its patented technology by registering additional improvements to the production process and coverage for incorporation of a range of biologically active molecules, peptides and amino acids.
The use of our SPF system in triple-negative breast cancer (4T1) and melanoma (B16-F10) models in mice showed a slowing of tumour growth and prolonged survival when compared to a placebo control arm (SPFs alone). Importantly, the system compares very favourably to other competitor products involving polymeric or sustained-release systems published in the literature and in clinical development.
Collaboration between CSIRO
and Cytomatrix Ltd
Cytomatrix has been conducting a polymer development and assessment program at CSIRO, Melbourne. The current phase is nearing completion with several targeted outcomes having very successfully completed:
Development of a new generation of short polymer fibres that will enable additional patent opportunities.
Demonstrated enhancement of RNA and DNA loading - up to 99% of targeted amount.
Demonstrated ability to manufacture SPFs using a range of different polymers, and to incorporate proteins, organic and inorganic molecules.
A deeper understanding of the factors affecting polymer degradation rates, enabling an extremely wide range to be achieved, from 5 days to 1.7 years.