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: $ 12.35万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=653667
• 关键词: Engineering; Starch; Based; Nanoparticles; Nanoparticle

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.

在多种情况下已经证明了使用纳米颗粒的药物来提高药物到达目标部位的**能力，尤其是在必须将药物**运送到细胞内的情况下，必须通过难以通过难以穿越的生物学障碍（例如，进入大脑或密集的组织或像tumor sumor sumor sumor sumor sumor sumor sumor sumor sumor）。淀粉纳米颗粒（SNP）是由我们的伴侣生态生物合成的，**在这种情况下具有在药物递送的潜力，鉴于它们在制造过程中有能力直接负载药物**，它们的尺寸极小，凝胶状样特性（因此**可能在压力下变形）以及生物学惰性。但是，使用SNP进行药物输送有两个**固有的局限性：（1）鉴于其多孔结构和（2）SNP的较小尺寸，同时是渗透到肿瘤中的**，也很快，也很快，也很少量，也可以诱发SNP相对快速地清除正常**循环**，从而限制SNPS SNPS的能力，从而限制了SNPS to Transpers of Tarms tots Tarms tots Tarmes tots Tarmess tots Tarmes to Tarmess tots Targes。在此提案中，**我们的目标是通过（1）工程SNP的表面来调整药物**的释放速率，以适应所需的值，以及（2）开发制造具有良好循环特性的受控簇的方法**可以选择性地降低药物释放**的循环特性（可以通过特定的化学在目标位点上的特定化学释放）（通过外部激活或以外部激活为特定时间）。我们预计，这种基于SNP的材料将不仅可以显着改善肿瘤内部和大脑内部和内部的药物的**递送（我们的两个**概念验证示范），还可以通过药物运输有效治疗**限制有效治疗的其他疾病。预计，这种能力既可以改善患有此类疾病的加拿大人的健康成果，又可以为** Ecosynthetix提供一个新的增值市场，以促进加拿大的新工作。