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Lyotropy as a Design Consideration for Ultra-Small Protein Nanoparticles via Electrohydrodynamic Jetting
Muhammad Haseeb Iqbal1, Julio Zelaya2, Quy Ong3
1Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Macromolecular Rapid Communications
|August 14, 2025
Summary
Researchers precisely engineered ultra-small protein nanoparticles using electrohydrodynamic jetting. Low salt concentrations enabled the creation of human serum albumin nanoparticles under 100 nm, crucial for nanomedicine delivery.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Protein-based nanoparticles offer distinct advantages over synthetic polymers in bioactivity and biodegradability.
- Precise control over nanoparticle physical properties, particularly size, is essential for effective nanomedicine delivery systems.
- Electrohydrodynamic (EHD) jetting is a key technique for engineering nanoparticle characteristics.
Purpose of the Study:
- To systematically understand and achieve the preparation of ultra-small human serum albumin (HSA) nanoparticles.
- To investigate the influence of salt concentration and type on nanoparticle size and distribution using EHD jetting.
- To establish precise control over nanoparticle size for optimized nanomedicine applications.
Main Methods:
- Utilized electrohydrodynamic (EHD) jetting for nanoparticle fabrication.
- Systematically varied salt concentrations (1-5 mM) and types during the EHD process.
- Analyzed nanoparticle size and distribution using dynamic light scattering or similar techniques.
Main Results:
- Successfully prepared human serum albumin (HSA) nanoparticles as small as 50 nm.
- Achieved narrow particle size distributions consistently below 100 nm with low salt concentrations (1-5 mM) and optimized EHD parameters.
- Demonstrated that anions modulate particle diameter according to the Hofmeister Series (SO4^2- < CO3^2- < H2PO4^- < Cl^- < I^-) at 2 mM concentration.
- Attributed size reduction to increased solution conductivity and interfacial charge density induced by salt ions, with high mobility ions compensating for surface energy.
Conclusions:
- Established a method for producing ultra-small protein nanoparticles (HSA) with controlled size and distribution via EHD jetting.
- Low salt concentrations significantly influence nanoparticle size, with anion type playing a role following the Hofmeister series.
- Precise control over ultra-small nanoparticle size is critical for targeted drug delivery, influencing tropism and cellular uptake.
