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 theability of drugs to get to their target sites, particularly in cases in which drugs must betransported inside cells to be functional and/or drug must be transported from the bloodthrough hard-to-penetrate biological barriers (e.g. into the brain or through dense tissues suchas tumour masses). Starch nanoparticles (SNPs), developed by our partner EcoSynthetix,have particular potential for drug delivery in this context given their capacity for direct loadingof drug during fabrication, their extremely small sizes, their gel-like properties (and thuspotential to deform under stress), and their biological inertness. However, there are twoinherent limitations to using SNPs for drug delivery: (1) drug release from SNPs is very fastgiven their porous structures and (2) the small size of SNPs, while ideal for penetrating intothe brain or deep into tumours, also induces relatively fast clearance of SNPs from normalcirculation, 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 drugrelease rates to desired values and (2) developing methods of fabricating controlled clustersof SNPs with good circulation properties that can be selectively degraded where drug releaseis desired (either by specific chemistry at the target site or by external activation after aspecific time). We anticipate that such SNP-based materials will significantly improve thedelivery of drugs not only deep inside tumours and both into and within the brain (our twoproof-of-concept demonstrations) but also other diseases in which effective therapy is limitedby drug transport. Such capacity is anticipated to both improve health outcomes forCanadians suffering from such diseases as well as provide a new, value-added market toEcoSynthetix that will promote new job creation in Canada.