Nanoparticle Encapsulation Technology
A patented system for encapsulating nanoscale therapeutics and gene editing machinery in nanoscale liposomes
The technology is a novel process technology that encapsulates therapeutics and nanoparticles into nanovesicles including liposomes and polymerosomes.
Liposomes are spherical vesicles composed of a lipid bilayer, with a central aqueous core. Within the aqueous water-filled core, drug therapeutics and other compounds or molecules - such as DNA, mRNA or proteins - can potentially be encapsulated with precision.
Once encapsulated, the properties of the lipid bilayer allows the drug or other compounds to be delivered across cell membranes and targeting intracellular regions of mammalian cells.
Alternatively, liposomes permit delivery of therapeutics to previously inaccessible areas of the body including biofilms, skin pores and within mucosa.
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The use of liposomes as therapeutic drug delivery agents is well established. However, their use for delivery of biotherapeutic agents such as proteins, DNA editing machinery, and bacteriophages has shortcomings.
The technology developed at Loughborough University by Dr Danish Malik overcomes current limitations in encapsulating such nanoparticles and has been demonstrated to encapsulate a range of nanoscale therapeutic cargoes.
The ability to encapsulate a broad range of therapeutic nanoparticles thus opens up diverse opportunities for novel potential therapeutic interventions that would benefit from the demonstrated delivery effectiveness of liposomes.
Current limitations in encapsulating nanoparticles in liposomes
Some of the limitations that the Loughborough technology overcomes are:
Low encapsulation efficiency
Current methods result in very low cargo titres of encapsulated nanoparticles that are insufficient for intended applications.
Inability to control for nanovesicle size
Current methods cannot encapsulate nanoscale particles effectively in nanoscale sized liposomes. Nanoscale liposomes (as opposed to micron scale liposomes) are required, due to size constraints for in-vivo cell targeting and trans-cell membrane delivery of nanoparticles.
Encapsulation regardless of particle charge or attaching covalently
For some nanoparticles such as DNA, RNA, plasmids the encapsulation ‘into’ lipoplexes/liposomes can only be achieved using a charge effect (eg using cationic lipids to ‘attach’ RNA molecules).Other methods to encompass nanoparticles involve covalent linking strategies.
The Loughborough technology templates the lipid nanovesicle around the nanoparticle and thus is completely independent of using any charge effects or covalent linking strategy. Indeed, the technology can theoretically encompass any nanoparticle or even combinations of nanoparticles (such as the CRISPR endonucleases).
Applications of the nanoparticle delivery technology
The application of the technology depends on the nature of the nanoparticle encompassed.
We have demonstrated that the technology can efficiently encompass bacteriophage, DNA, RNA, and proteins.
Envisaged applications are:
The treatment of intracellular infections
The technology could be used to treat intracellular infections - including tuberculosis, listeria, salmonella and typhoid - by delivering bacteriophages intracellularly.
Additional information is available in the Nanoparticle Encapsulation Technology document below.
The treatment of bacterial pathogenesis
The technology could be used to treat bacterial pathogenesis associated with biofilms and mucosa by encompassing bacteriophage.
Additional information is available in the Nanoparticle Encapsulation Technology document below.
Delivering gene editing machinery
The technology could be used to deliver gene editing machinery such as the Crispr Cas9 system, TALENs, DNA and RNA to attenuate genetic disorders or to treat cancer in-vivo.
It could administer the encapsulated genetic machinery to sites of cancer that are easily accessible such as to the skin or lungs, or targeting moieties could be added to the liposome to enable targeting to specific cell types in the body.
Furthermore, the technology can be used to faithfully prepare multi-lamellar or multi-vesicle liposomes that could be used to target cells and following this to target specific compartments or organelles.
As a non-viral method of cell transfection / genetic modification in-vitro
Viral methods of genetic modification / genetic modification suffer from various issues, including low efficiency and concerns over deleterious artifacts affecting the cell.
Similarly non-viral methods such as electroporation, although efficient, also suffer from concerns over deleterious artefacts.
In contrast the liposomal delivery of genetic modification machinery is safe, highly efficient and with no envisaged deleterious effects to cell physiology or genetic code.
Also, more than one nanoparticle can be encompassed thereby offering more complex interventions and outcomes. We envisage the main applications in this space will be for genetically modifying CarT cells for cancer therapy, and its use for routine genetic modification in research and development.
Current technology status
The technology is protected through a patent application.
We have attained proof of concept for bacteriophage delivery into cells and into mucosal/biofilm sites.
We are looking for commercialisation partners to take the technology forward for further proof of concept validation and for licensing.
If you are interested in learning more about this technology with a view to collaborative development, licensing, or investment - please get in touch.
