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基于聚(己内酯)和硅粒子的可注射温敏纳米复合材料用于亲水性和疏水性药物的局部释放。

Injectable Thermosensitive Nanocomposites Based on Poly(-vinylcaprolactam) and Silica Particles for Localized Release of Hydrophilic and Hydrophobic Drugs.

机构信息

Interdisciplinary Laboratory of Electrochemistry and Ceramics (LIEC), Departament of Chemistry, Federal University of São Carlos (UFSCar), Rod. Washington Luis km 235, CP 676 São Carlos, São Paulo 13565-905, Brazil.

Laboratory of Applied Immunology, Federal University of São Carlos (UFSCar), São Carlos, Rod. Washington Luis km 235, CP 676 São Carlos, São Paulo 13565-905, Brazil.

出版信息

Langmuir. 2023 Feb 14;39(6):2380-2388. doi: 10.1021/acs.langmuir.2c03160. Epub 2023 Feb 6.

Abstract

The systemic delivery of drugs employed by conventional methods has shown to be less effective than a localized delivery system. Many drugs have the effectiveness reduced by fast clearance, increasing the amount required for an efficient treatment. One way to overcome this drawback is through the use of thermoresponsive polymers that undergo a sol-gel transition at physiological temperature, allowing their injection directly in the desired site. In this work, thermosensitive nanocomposites based on poly(-vinylcaprolactam) and silica particles with 80 and 330 nm were synthesized to be employed as delivery systems for hydrophobic (naringin) and hydrophilic (doxorubicin hydrochloride) drugs. The insertion of SiO increased the rheological properties of the nanocomposite at 37 °C, which helps to prevent its diffusion away from the site of injection. The synthesized materials were also able to control the drug release for a period of 7 days under physiological conditions. Due to its higher hydrophobicity and better interaction with the PNVCL matrix, naringin presented a more controlled release. The Korsmeyer-Peppas model indicated different release mechanisms for each drug. At last, a preliminary study of DOX-loaded nanocomposites cultured with L929 and MB49 cells showed negligible toxic effects on healthy cells and better efficient inhibition of carcinoma cells.

摘要

传统方法的药物全身给药效果不如局部给药系统。许多药物由于快速清除而降低了疗效,需要增加剂量才能达到有效的治疗效果。克服这一缺点的一种方法是使用热响应性聚合物,它们在生理温度下经历溶胶-凝胶转变,允许直接在所需部位注射。在这项工作中,合成了基于聚(己内酯)和 80nm 和 330nm 二氧化硅颗粒的温敏纳米复合材料,用作疏水性(柚皮苷)和亲水性(盐酸多柔比星)药物的给药系统。SiO 的插入增加了纳米复合材料在 37°C 时的流变性能,有助于防止其从注射部位扩散。在生理条件下,合成材料还能够控制药物释放 7 天。由于其较高的疏水性和与 PNVCL 基质更好的相互作用,柚皮苷的释放更具可控性。Korsmeyer-Peppas 模型表明,每种药物的释放机制都不同。最后,对用 L929 和 MB49 细胞培养的载 DOX 纳米复合材料进行的初步研究表明,对健康细胞几乎没有毒性作用,对癌细胞的抑制作用更好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7465/9933531/af14082e60ed/la2c03160_0002.jpg

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