Engineering Starch-Based Nanoparticles and Nanoparticle Clusters for Improving Local Drug Delivery to Tumour Cores and the Brain

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Delivering drugs using nanoparticles has been demonstrated in multiple cases to improve the**ability of drugs to get to their target sites, particularly in cases in which drugs must be**transported inside cells to be functional and/or drug must be transported from the blood**through hard-to-penetrate biological barriers (e.g. into the brain or through dense tissues such**as tumour masses). Starch nanoparticles (SNPs), developed by our partner EcoSynthetix,**have particular potential for drug delivery in this context given their capacity for direct loading**of drug during fabrication, their extremely small sizes, their gel-like properties (and thus**potential to deform under stress), and their biological inertness. However, there are two**inherent limitations to using SNPs for drug delivery: (1) drug release from SNPs is very fast**given their porous structures and (2) the small size of SNPs, while ideal for penetrating into**the brain or deep into tumours, also induces relatively fast clearance of SNPs from normal**circulation, restricting the capacity of SNPs to transport drugs to target sites. In this proposal,**we aim to address these challenges by (1) engineering the surface of SNPs to adjust drug**release rates to desired values and (2) developing methods of fabricating controlled clusters**of SNPs with good circulation properties that can be selectively degraded where drug release**is desired (either by specific chemistry at the target site or by external activation after a**specific time). We anticipate that such SNP-based materials will significantly improve the**delivery of drugs not only deep inside tumours and both into and within the brain (our two**proof-of-concept demonstrations) but also other diseases in which effective therapy is limited**by drug transport. Such capacity is anticipated to both improve health outcomes for**Canadians suffering from such diseases as well as provide a new, value-added market to**EcoSynthetix that will promote new job creation in Canada.