Ionizable lipids in bio-inspired nanocarriers

Area of Science:

• Biophysics
• Nanotechnology
• Materials Science

Background:

• Bio-inspired nanoparticles, particularly lipid nanoparticles (LNPs), are crucial in various applications.
• Optimizing LNP composition often involves incorporating ionizable lipids to control charge and potential distributions.
• Understanding these distributions is key to predicting LNP behavior and efficacy.

Purpose of the Study:

• To develop a generic statistical model for describing charge and potential distributions within LNPs containing ionizable lipids.
• To investigate the influence of ionizable lipids and solution ionic strength on the internal LNP potential.
• To elucidate the mechanisms of charge neutralization within LNPs.

Main Methods:

• A generic statistical model was employed, considering LNPs with biophase regions and interphase boundaries.
• The model integrates the Langmuir-Stern equation for ionizable lipids and the Poisson-Boltzmann equation for other charges.
• The Poisson-Boltzmann equation was also applied to describe the potential outside the LNP.

Main Results:

• The model predicts a low internal LNP potential, typically smaller than or about [Formula: see text].
• Potential changes are predominantly observed near the LNP-solution interface.
• Charge neutralization of ionizable lipids occurs mainly due to solution ions, with dissociation-mediated neutralization being less significant internally.

Conclusions:

• The internal potential of LNPs is largely confined to the interface region.
• Solution ionic strength plays a dominant role in neutralizing ionizable lipids within LNPs.
• This understanding aids in the rational design and application of ionizable lipid-based nanoparticles.