2. Academic Validation
  3. Flash nanoprecipitation allows easy fabrication of pH-responsive acetalated dextran nanoparticles for intracellular release of payloads

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

  • Discov Nano. 2024 Jan 4;19(1):4. 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 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, 26505, USA.
  • 2 Department of Clinical Pharmacy, West Virginia University School of Pharmacy, Morgantown, WV, 26505, USA.
  • 3 Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 4 Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, 26505, USA.
  • 5 Department of Physiology, Pharmacology and Toxicology, West Virginia University, Morgantown, WV, 26505, USA.
  • 6 Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, 26505, USA.
  • 7 Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, 26505, USA. sharan.bobbala@hsc.wvu.edu.
PMID: 38175336 DOI: 10.1186/s11671-023-03947-w
Abstract

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. 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.

Keywords

Dextran; Flash nanoprecipitation; Intracellular release; Nanoparticles; Surfactants; pH-responsive.

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