Nanopore and Nanoparticle Formation with Lipids Undergoing Polymorphic Phase Transitions

Abstract

We describe several unexpected phenomena, caused by a solid-solid phase transition (gel-tocrystal) typical for all main classes of lipid substancesphospholipids, 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 lipidin-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.

Cold-Burst Method for Nanoparticle Formation with Natural Triglyceride Oils

“…100 μm to 0.4 μm after one cooling and heating cycle only of the lipid dispersion, see Figure 1 and Movie 1 for illustrative examples. 7 Briefly, the mechanism of the cold-burst process is the following. Upon fast cooling, many lipids, e.g.…”

“…In other words, after the α→β phase transition, the lipid phase acquires internal structure of crystalline domains, separated by nanoporous network. 7 The formed nanovoids were reported to have reduced pressure (so-called "negative pressure effect"). [12][13][14] In aqueous surfactant solutions, this negative pressure sucks the surrounding aqueous phase.…”

“…[12][13][14] In aqueous surfactant solutions, this negative pressure sucks the surrounding aqueous phase. 7 Depending on the specific surfactants, upon storage or upon heating, the lipid particles increase their volume and, finally, each of them disintegrates (bursts) into millions of smaller particulates. 7 In our previous study we found that the cold-burst process is observed with surfactants ensuring low three-phase contact angle at the solid triglyceride-water-air contact line, ca.…”

“…3 in Ref. [7]. (b) Illustration of the cold-burst as observed with trilaurin drops (C12TG) dispersed in aqueous solution of 1.5 wt.…”

Kinetic Study on Alpha-Form Crystallization of Mixed-Acid Triacylglycerols POP, PPO, and Their Mixture

“…The crystallization behavior of TAGs has been studied from the perspective of fundamental aspects and applications in a polymorph-dependent manner [2][3][4]. For example, solid lipid nanoparticles (SLNs) have been studied as carriers of functional substances in pharmaceuticals [5][6][7] and foods [8,9], where the polymorphism of nanostructured lipid crystals is closely related to their functionality, such as loading ability and release control. In particular, the controlled preparation of TAG crystalline particles of the metastable α polymorph is highly effective for the delivery of active drug substances.…”