Nanopore and nanoparticle formation with lipids, undergoing polymorphic phase transitions

TL;DR

This study reveals that lipid phase transitions induce nanopore formation, leading to spontaneous nanoparticle creation and emulsification, which can be optimized and scaled for drug delivery applications.

Contribution

It uncovers the mechanism of nanopore formation during lipid phase transitions and demonstrates a scalable method for producing drug-loaded nanoparticles.

Findings

Lipid phase transitions cause nanopore networks to form.

Water impregnation floods nanopores, fracturing lipids into nanoparticles.

The process is effective with high drug loads and scalable.

Abstract

We describe several unexpected phenomena, caused by a solid-solid phase transition (gel-to-crystal) typical for all main classes of lipid substances - phospholipids, triglycerides, diglycerides, alkanes, etc. We discovered that this transition leads to spontaneous formation of a network of nanopores, spreading across the entire lipid structure. These nanopores are spontaneously impregnated (flooded) by water when appropriate surfactants are present, thus fracturing the lipid structure at a nano-scale. As a result, spontaneous disintegration of the lipid into nanoparticles or formation of double emulsions is observed, just by cooling and heating of an initial coarse lipid-in-water dispersion around the lipid melting temperature. The process of nanoparticle formation is effective even after incorporation of medical drugs of high load, up to 50 % in the lipid phase. The role of the main governing factors is clarified, the procedure is optimized, and the possibility for its scaling-up to industrially relevant amounts is demonstrated.