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

工程化淀粉基纳米粒子和纳米粒子簇以改善肿瘤核心和大脑的局部药物输送

• 批准号: 508393-2017
• 负责人: Hoare, Todd
• 金额: $ 5.18万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=621899
• 关键词: Engineering; Starch; Based; Nanoparticles; Nanoparticle

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.

使用纳米颗粒递送药物已经在多个病例中被证明可以提高药物到达其靶位点的能力，特别是在药物必须在细胞内转运才能发挥功能和/或药物必须从血液中转运通过难以穿透的生物屏障（例如进入大脑或通过致密组织如肿瘤块）的情况下。由我们的合作伙伴EcoSynthetix开发的淀粉纳米颗粒（SNP）在这种情况下具有特殊的药物递送潜力，因为它们在制造过程中具有直接装载药物的能力，它们的极小尺寸，它们的凝胶状特性（因此在应力下可能变形）以及它们的生物惰性。然而，使用SNPs进行药物递送存在两个固有的限制：（1）考虑到SNPs的多孔结构，药物从SNPs中释放非常快，以及（2）SNPs的小尺寸虽然对于渗透到大脑或深入肿瘤是理想的，但也会导致SNPs从正常循环中相对较快的清除，限制了SNPs将药物转运到靶位点的能力。在这项提案中，我们的目标是通过以下方式来解决这些挑战：（1）设计SNP的表面，以将药物释放速率调节到所需的值;（2）开发制造具有良好循环特性的SNP受控簇的方法，这些SNP簇可以在需要药物释放的地方选择性降解（通过靶位点的特定化学反应或在特定时间后通过外部活化）。我们预计，这种基于SNP的材料将显着改善药物的递送，不仅深入肿瘤内部，进入大脑和大脑内（我们的两个概念验证演示），而且还包括其他疾病，其中有效的治疗受到药物运输的限制。预计这种能力将改善患有此类疾病的加拿大人的健康状况，并为EcoSynthetix提供一个新的增值市场，这将促进加拿大创造新的就业机会。