Food Grade Nanodelivery Systems of Phytochemicals for Prevention of Colorectal Cancer

用于预防结直肠癌的食品级植物化学物质纳米递送系统

• 批准号: 8968586
• 负责人: Qixin Zhong
• 金额: $ 10.2万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8968586
• 关键词: Address; Adverse effects; Antioxidants; Apigenin; Biochemical; Biological; Biological Models; Biopolymers; Blood; Calcium; Cancer Patient; Caseins; Characteristics; Chemicals; Chitosan; Colon; Colorectal Cancer; Cultured Cells; Curcumin; Data; Diet; Digestion; Dimethyl Sulfoxide; Disease; Drug Delivery Systems; Encapsulated; Equipment; Exhibits; Flow Cytometry; Food; Goals; Gum Arabic; HCT116 Cells; Health; Human; Immune system; In Vitro; Intervention; Intestinal Polyps; Lead; Magnetism; Malignant Neoplasms; Methods; Modeling; Mucous Membrane; NMR Spectroscopy; Nanotechnology; Organic solvent product; Pectins; Phytochemical; Polysaccharides; Prevention; Process; Property; Proteins; Public Health; Science; Shapes; Sodium; Solid; Solutions; Soybeans; Surface; System; Techniques; Testing; Viscosity; Visible Radiation; Work; absorption; anticancer activity; anticancer treatment; base; cancer cell; cancer prevention; colorectal cancer prevention; cost; experience; functional food; improved; in vitro activity; in vivo; in vivo Model; innovation; mouse model; nanocapsule; nanoencapsulated; nanofabrication; nanomaterials; nanoparticle; novel; prevent; public health relevance; research study; uptake

 DESCRIPTION (provided by applicant): Many food-sourced phytochemicals have strong anticancer activities and can be used as safe anticancer treatment or prevention agents. Many phytochemicals however are lipophilic and are unstable. Although they have strong antioxidant activities and effectively inhibit the proliferation of cancer cells in vitro, the in vivo anticancr activities are typically much lower. Furthermore, despite many delivery systems studied for phytochemicals, few are practical due to limitations in the use of synthetic encapsulation materials, the use of organic solvents and the scalability of processes. The goal of this proposal is to fabricate nanodelivery systems of lipophilic phytochemicals based on food biopolymers for use of functional foods in cancer prevention. In ongoing experiments, dissolving curcumin in a pH 12.0 dairy protein (sodium caseinate) solution and subsequent neutralization using a magnetic stir plate effectively encapsulated curcumin as nanoparticles. The treatments did not cause the degradation of curcumin, and the nanoencapsulated curcumin showed much improved anti-proliferation activity against HCT-116 cells than curcumin pre-dissolved in dimethylsulfoxide. The preliminary data suggest the innovation of low-cost, food grade nanodelivery systems for some lipophilic phytochemicals fabricated with easily scalable processes without the need of specialized equipment, organic solvent, and synthesized/modified materials. Based on the preliminary findings using curcumin, we hypothesize that in vivo anticancer activity of lipophilic phytochemicals can be enhanced by nanoencapsulation in food biopolymers using the above low-cost, low- energy, and organic solvent-free processes. The hypothesis will be tested in two specific aims: 1) conditions of nano-encapsulating lipophilic phytochemicals will be studied using sodium caseinate and two low-viscosity surface-active polysaccharides (gum arabic and soluble soybean polysaccharide) as representative digestible and indigestible food biopolymers. [Casein nanocapsules will be encapsulated in chitosan/calcium pectinate composite microparticles for selective release in the colon.] Curcumin and apigenin will be used as two model lipophilic phytochemicals. Physicochemical properties of nanoparticles, properties related to nanoencapsulation, and in vitro anticancer activities of nanoencapsulated curcumin and apigenin will be characterized using various techniques. 2) in vitro anticancer activities of nano-encapsulated apigenin will be confirmed by in vivo models. The innovation of low-cost, food biopolymer-based nanoencapsulation method addresses the priority of "paradigm-shifting approaches to nanomaterials fabrication for cancer applications that could lead, e.g., to improved control of size, shape, surface characteristics, and lower fabrication costs" in the previous RFA PA-11- 149. The safe and affordable delivery systems enable the use of phytochemicals as cancer prevention agents in functional foods applications or as cancer curing agents. The elimination of synthetic materials and organic solvents can reduce the side effects and complications for cancer patients with weakened immune systems.

 描述（由适用提供）：许多食物外源具有强大的抗癌活性，可以用作安全的抗癌治疗或预防剂。但是，许多物理学是亲脂性的，并且不稳定。尽管它们具有强大的抗氧化活性，并有效地抑制了癌细胞在体外的增殖，但体内抗癌活性通常要低得多。此外，为植物化学物质进行许多递送系统研究，由于合成封装材料的使用局限性，有机溶液的使用和过程可扩展性，因此很少有实用性。该提案的目的是基于食品生物聚合物的亲脂性植物化学物质的纳米传递系统，用于预防癌症。在正在进行的实验中，将姜黄素溶解在pH 12.0奶制蛋白（酪蛋白钠）溶液中，然后使用有效封装的姜黄素作为纳米颗粒的磁性搅拌板进行中和。这些处理并未引起姜黄素的降解，而纳米封装的姜黄素比在二甲基硫氧化二甲基硫化的姜黄素中表现出对HCT-116细胞的抗增殖活性的改善。初步数据表明，对于一些易于易于扩展工艺而制造的亲脂性植物化学物质的低成本，食品级纳米传递系统的创新，而无需专业设备，有机溶解度和合成/修改的材料。基于使用姜黄素的初步发现，我们假设使用上述低成本，低能量和有机溶液的生物聚合物在食品生物聚合物中，可以通过纳米囊化来增强亲脂性植物化学物质的体内抗癌活性。该假设将以两个具体的目的进行检验：1）使用Caseinate钠和两个低粘度的表面活性多糖（Abum Arabic和soluuble大豆多糖）使用纳米封装的亲脂性植物化学物质的条件，以代表可消化和土著食品，并代表可消化的食物。 [酪蛋白纳米胶囊将封装在壳聚糖/丁香钙的复合微粒中，用于在结肠中选择性释放。纳米颗粒的物理化学特性，与纳米囊化有关的特性以及纳米封装的姜黄素和猿猴的体外抗癌活性将使用各种技术来表征。 2）体内模型将证实纳米封装的阿apigenin的体外抗癌活性。低成本，基于食物的基于食物的纳米囊化方法的创新旨在解决“用于纳米材料制造的范式转移方法的优先级，用于癌症应用，例如，可以改善对尺寸，形状，表面特征的控制，以改善以前的RFA PA11-11-149的癌症。应用或癌症课程代理。消除合成材料和有机溶液可以减少免疫系统疲软的癌症患者的副作用和并发症。