Targeted Drug Delivery
Gene Silencing
Canine Cancers
Principle Charateristics

Non living

Membrane-bound cytoplasm derived from bacteria.

No potential to replicate or be virulent in vivo.

Anucleate

Does not carry DNA from the parent biological source.

Cannot gather mutations in the endogenous genome, cannot reproduce.

Nanosize

400nm diameter nanocell.

Can escape blood stream through the leaky vasculature and into the tumour micro-environment without extravasating into normal tissues.

Tough outer membrane

Surrounded by a rigid and stable biological membrane.

Unlike liposomes, the EDVs do not fall apart or leak in the extracellular environment. ie there is minimal to no toxicity from its payload of toxic chemotherapeutic drug or siRNA.

Versatile delivery system

Readily packaged with a wide range of different anti-cancer therapeutics e.g. (hydrophilic, hydrophobic, amphipathic e.g. Doxorubicin, Paclitaxel, Vinblastine, 5-Fluorouracil, Irinotecan, Cisplatin etc), plasmid DNAs and siRNAi sequences.

No EDV modifications for each therapeutic are necessary unlike liposomal and synthetic nanoparticle/polymer vectors.

Easy loading

The process of payload packaging is easily accomplished.

Quick and cost-effective.

High payload accommodation

Can package 1 million to 10 million drug molecules per EDV, at least 12,000 siRNA molecules and ~ 100 copies of plasmid.

Liposomal drug carriers like liposomal doxorubicin can only package 10,000 doxorubicin molecules per particle.
Antibodies and aptamers carry less than 10 and 2,000 siRNA molecules, respectively.

Cancer cell targeting

EDVs are targeted to cancer cells in vivo by virtue of a bispecific antibody where one arm carries anti-EDV specificity and the other arm has specificity to a tumour cell-surface antigen of choice e.g. EGFR, HER2/neu etc.

Binding is multivalent and of high affinity to ensure that the antibody does not dissociate from the EDV in vivo. Passive targeting occurs when EDVs drop out into the tumour micro-environment and then specific targeting by virtue of the targeting antibody.

Safety

No toxicities in various animals including monkeys, dogs and pigs.

Potential for combination of cancer drugs and high therapeutic index. Repeat dosing not a problem.

Stability

Drug or siRNA/shRNA or plasmid packaged, BsAb-targeted EDVs can be readily lyophilised and stored for at least 6 months  at room temperature without loss
of structural or functional characteristics or
therapeutic efficacy.

Lyophilised EDVs have been shipped to various parts of the world and shown to be identical to freshly prepared EDVs