For manufacturers seeking drug approval for controlled release therapeutics using liposomes and LNPs, stability under shelf and in vivo conditions has been a problem to date. This is particularly true if the API is released in unintended ways and locations through changes in temperature, pH or shear stress, particle fission & fusion, lipid oxidation and hydrolysis, leakage; and loss of hydrophilic cargoes. Control of the interaction between phospholipids and water molecules, is key to making liposomes and LNP structures with the desired morphology, encapsulation efficiency, stability and size. The FDA’s “Guidance for Industry” concerning liposome drug products emphasises the importance of size and size distribution as “critical quality attributes and essential components for stability.
Currently there are five main methods of making liposomes at lab scale, allowing for size control from around 20nm up to several microns and composing of one or more bilayers, and a smaller number of larger-scale techniques. However, all of these techniques have the potential to degrade the efficacy of APIs due to the application of mechanical stresses (e.g. high shear, sonication, high pressure, etc.), use of unsuitable chemicals (e.g. volatile organic solvents, etc.), or by producing extremes of pH. Commercially available high temperature methods, in which the lipids are heated to around 80oC, exemplify the challenges towards more widespread approval and uptake of these drug delivery systems.
Recent work by Micropore Technologies has demonstrated that their aseptic membrane-based technology, already used for the formation near mono-dispersed PLGA microspheres, can equally be used as a refined micro-mixer for liposome and lipid nanoparticle production. By enabling the mixing of two miscible liquids together in a controlled manner achieving very narrow size distribution at, or below, room temperature, damage from high temperatures, pressure or shear can effectively be eliminated. LEARN MORE
An article by VANESSA ZAINZINGER for Chemistry World