A redox-responsive delivery system for paclitaxel based on heparin—pluronic F127 nanogel

IF 2.1 4区 材料科学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Nguyen T. Huong, Nguyen T. N. Hoi, Mac D. Hung, Le M. Tri, Nguyen V. Hung, Le D. Anh, Vu T. Dong, Ly Q. Vuong, Vu M. Thanh
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Abstract

Paclitaxel (PTX), a chemo-drug widely used in cancer chemotherapy for a variety of tumors, has been still faced with several problems in therapeutic applications due to its poor water solubility, low content in natural sources, expensive multistep processes of synthesis and side effects. In this study, a nanogel system based on the conjugation of Heparin and Pluronic F127 via disulphide bridges was developed for PTX delivery in a redox responsive way to over these mentioned drawbacks. The obtained Hep-F127 system were proved and characterized through H-NMR, zeta potential, DLS, TEM and FT-IR methods. TEM result showed that the nanogel Hep-F127 was spherical, non-agglomerated and relatively uniform with an average particle diameter of 80 nm. PTX was effectively encapsulated into the nanogel thanks to poly(propylene oxide) (PPO) units of F127 molecules with DLE and DLC values of about 92% and 18%, respectively. Meanwhile, the nanogel was stable in physiological condition but broken under reducing condition, leading to a well-controlled release in physiological condition and a fast release in simulating tumor-microenvironmental condition. This contributed to reducing side effects and increasing the effectiveness of treatment of PTX. In addition, cytotoxicity of Hep-F127 and PTX@Hep-F127 was in vitro tested on the L929 cell line. This study suggested that the nanogel Hep-F127 would to be a promising carrier for enhancing the solubility of PTX and release PTX in a redox-responsive way in cancer treatment.

Abstract Image

基于肝素- pluronic F127纳米凝胶的紫杉醇氧化还原反应递送系统
紫杉醇(Paclitaxel, PTX)是一种广泛应用于多种肿瘤化疗的化疗药物,但由于其水溶性差、天然来源含量低、合成过程昂贵、副作用大等问题,在治疗应用中仍面临诸多问题。在这项研究中,一种基于肝素和Pluronic F127通过二硫桥偶联的纳米凝胶系统被开发出来,用于以氧化还原响应的方式递送PTX,以克服上述缺点。通过H-NMR、zeta电位、DLS、TEM和FT-IR等方法对所得Hep-F127体系进行了验证和表征。TEM结果表明,Hep-F127纳米凝胶呈球形,无团聚,相对均匀,平均粒径为80 nm。由于F127分子的聚环氧丙烷(PPO)单元的DLE和DLC值分别约为92%和18%,PTX被有效地封装到纳米凝胶中。同时,纳米凝胶在生理条件下稳定,在还原条件下破裂,生理条件下释放控制良好,在模拟肿瘤微环境条件下释放快速。这有助于减少副作用,提高PTX治疗的有效性。此外,我们还在体外测试了Hep-F127和PTX@Hep-F127对L929细胞株的细胞毒性。本研究提示,纳米凝胶Hep-F127有望成为提高PTX溶解度并以氧化还原反应方式释放PTX的载体。
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来源期刊
Journal of Nanoparticle Research
Journal of Nanoparticle Research 工程技术-材料科学:综合
CiteScore
4.40
自引率
4.00%
发文量
198
审稿时长
3.9 months
期刊介绍: The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size. Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology. The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
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