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两亲性纳米载体作为胰岛素传递的潜在载体。

Catanionic nanocarriers as a potential vehicle for insulin delivery.

机构信息

Instituto para el Desarrollo Agroindustrial y de la Salud (IDAS, UNRC-CONICET), Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, X5804ZAB, Río Cuarto, Córdoba, Argentina; Departamento de Química. Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, X5804ZAB, Río Cuarto, Córdoba, Argentina; Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, X5804ZAB, Río Cuarto, Córdoba, Argentina.

Instituto de Biotecnología Ambiental y Salud (INBIAS, UNRC-CONICET), Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, X5804ZAB, Río Cuarto, Córdoba, Argentina; Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, X5804ZAB, Río Cuarto, Córdoba, Argentina.

出版信息

Colloids Surf B Biointerfaces. 2020 Apr;188:110759. doi: 10.1016/j.colsurfb.2019.110759. Epub 2019 Dec 24.

Abstract

Diabetes is a disease that affects millions of people in the World, constituting a global problem. Patients are administered insulin subcutaneous injections, resulting in high costs and frequent infections in the injection site. A possible solution to this problem may be the use of nanotechnology. Nanotransporters can act as specific release systems able to overcome the current limitations to drug delivery. Liposomes and vesicles can deliver drugs directly and efficiently to the site of action, decreasing toxicity and adverse effects. In previous studies, we demonstrated the biocompatibility and safety of catanionic benzyl n-hexadecyldimethylammonium 1,4 -bis-2-ethylhexylsulfosuccinate (BHD-AOT) vesicles using both in vitro and in vivo tests. Thus, the aims of this work were to evaluate the ability of the BHD-AOT vesicles to encapsulate insulin; to analyze the structural properties and stability of the system, vesicle-Insulin (VIn), at different pH conditions; and to study the ability of VIn to decrease the glycemia in miceby different administration routes. Our results showed that 2 and 5 mg mL of vesicles were able to encapsulate about 55 % and 73 % of insulin, respectively. The system VIn showed a significant increase in size from 120 to 350 nm, changes in the surface zeta potential value, and high stability to different pH conditions. A significant decrease of the glycemia after VIn administration was demonstrated in in vivo assays, including the oral route. Our results reveal that BHD-AOT vesicles may be an appropriate system to encapsulate and protect insulin, and may be a potential system to be administrated in different ways as an alternative strategy to conventional therapy.

摘要

糖尿病是一种影响全球数百万人的疾病,构成了一个全球性问题。患者接受皮下胰岛素注射,导致成本高昂且注射部位频繁感染。这个问题的一个可能的解决方案可能是利用纳米技术。纳米转运体可以作为特定的释放系统,能够克服药物输送的当前限制。脂质体和囊泡可以直接有效地将药物递送到作用部位,降低毒性和不良反应。在之前的研究中,我们使用体外和体内试验证明了两性离子苄基十六烷基二甲基铵 1,4-双-2-乙基己基磺基琥珀酸盐(BHD-AOT)囊泡的生物相容性和安全性。因此,本工作的目的是评估 BHD-AOT 囊泡包封胰岛素的能力;分析在不同 pH 条件下系统囊泡-胰岛素(VIn)的结构特性和稳定性;并研究 VIn 通过不同给药途径降低小鼠血糖的能力。我们的结果表明,2 和 5mg·mL 的囊泡分别能够包封约 55%和 73%的胰岛素。VIn 系统的粒径从 120nm 显著增加到 350nm,表面 zeta 电位值发生变化,并且在不同 pH 条件下具有高稳定性。体内实验表明,VIn 给药后血糖显著降低,包括口服途径。我们的结果表明,BHD-AOT 囊泡可能是一种合适的系统,可以包封和保护胰岛素,并且可能是一种潜在的系统,可以作为传统治疗的替代策略,以不同的方式给药。

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