Flash nanoprecipitation allows easy fabrication of pH-responsive acetalated dextran nanoparticles for intracellular release of payloads,Nanoscale Research Letters

当前位置： X-MOL 学术 › Nanoscale Res. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Flash nanoprecipitation allows easy fabrication of pH-responsive acetalated dextran nanoparticles for intracellular release of payloads
Nanoscale Research Letters ( IF 5.5 ) Pub Date : 2024-01-04 , DOI: 10.1186/s11671-023-03947-w
Krystal A Hughes ₁ , Bishal Misra ₁ , Maryam Maghareh ₂ , Parinya Samart _{1,

3} , Ethan Nguyen ₁ , Salik Hussain _{4,

5} , Werner J Geldenhuys _{1,

6} , Sharan Bobbala ₁

Affiliation

Acetalated dextran (Ac-Dex) nanoparticles are currently of immense interest due to their sharp pH-responsive nature and high biodegradability. Ac-Dex nanoparticles are often formulated through single- or double-emulsion methods utilizing polyvinyl alcohol as the stabilizer. The emulsion methods utilize toxic organic solvents such as dichloromethane or chloroform and require multi-step processing to form stable Ac-Dex nanoparticles. Here, we introduce a simple flash nanoprecipitation (FNP) approach that utilizes a confined impinging jet mixer and a non-toxic solvent, ethanol, to form Ac-Dex nanoparticles rapidly. Ac-Dex nanoparticles were stabilized using nonionic PEGylated surfactants, D-α-Tocopherol polyethylene glycol succinate (TPGS), or Pluronic (F-127). Ac-Dex nanoparticles formed using FNP were highly monodisperse and stably encapsulated a wide range of payloads, including hydrophobic, hydrophilic, and macromolecules. When lyophilized, Ac-Dex TPGS nanoparticles remained stable for at least one year with greater than 80% payload retention. Ac-Dex nanoparticles were non-toxic to cells and achieved intracellular release of payloads into the cytoplasm. In vivo studies demonstrated a predominant biodistribution of Ac-Dex TPGS nanoparticles in the liver, lungs, and spleen after intravenous administration. Taken together, the FNP technique allows easy fabrication and loading of Ac-Dex nanoparticles that can precisely release payloads into intracellular environments for diverse therapeutic applications.

Graphical abstract

pH-responsive Acetalateddextran can be formulated using nonionic surfactants, such as TPGS or F-127, for intracellular release of payloads. Highly monodisperse and stable nanoparticles can be created through the simple, scalable flash nanoprecipitation technique, which utilizes a confined impingement jet mixer.

中文翻译：

快速纳米沉淀可以轻松制造 pH 响应性乙缩醛化葡聚糖纳米粒子，用于细胞内释放有效负载

乙酰化右旋糖酐 (Ac-Dex) 纳米粒子目前因其敏锐的 pH 响应性和高生物降解性而引起了极大的兴趣。 Ac-Dex 纳米粒子通常使用聚乙烯醇作为稳定剂通过单乳液或双乳液方法配制。乳液法使用二氯甲烷或氯仿等有毒有机溶剂，需要多步处理才能形成稳定的 Ac-Dex 纳米颗粒。在这里，我们介绍了一种简单的快速纳米沉淀 (FNP) 方法，该方法利用受限冲击喷射混合器和无毒溶剂乙醇快速形成 Ac-Dex 纳米粒子。使用非离子聚乙二醇化表面活性剂、D-α-生育酚聚乙二醇琥珀酸酯 (TPGS) 或 Pluronic (F-127) 稳定 Ac-Dex 纳米颗粒。使用 FNP 形成的 Ac-Dex 纳米粒子具有高度单分散性，并且稳定地封装了多种有效负载，包括疏水性、亲水性和大分子。冻干后，Ac-Dex TPGS 纳米粒子可保持稳定至少一年，有效负载保留率超过 80%。 Ac-Dex 纳米粒子对细胞无毒，并实现有效负载在细胞内释放到细胞质中。体内研究表明，静脉注射后，Ac-Dex TPGS 纳米颗粒主要在肝脏、肺和脾脏中生物分布。总而言之，FNP 技术可以轻松制造和加载 Ac-Dex 纳米颗粒，从而可以精确地将有效负载释放到细胞内环境中，用于多种治疗应用。