Lyotropic liquid crystalline nanoparticles are nanoscale self-assembled structures with internal cubic or hexagonal liquid crystalline organization. Their dispersions, cubosomes and hexosomes, are formed through the self-assembly of specific amphiphilic lipids in an aqueous environment and have attracted significant interest as advanced drug delivery systems. These liquid crystalline nanoparticles offer multiple advantages, including the encapsulation of hydrophilic, hydrophobic, and amphiphilic compounds, protection of active ingredients against hydrolysis and enzymatic degradation, sustained release of compounds, and cost-efficient production; and depending on the choice of components, non-toxicity, biocompatibility, and biodegradability.
Within the master’s thesis, our goal was to optimize the »bottom-up« preparation method for lyotropic liquid crystalline nanoparticle dispersions composed of glycerol monooleate in phosphate or acetate buffer, and poloxamer 407 as a stabilizer. This low-energy and simple method requires the use of a hydrotrope to enhance lipid solubility in the aqueous medium. To optimize the method, we systematically varied the parameters, i.e. composition of the anhydrous mixture (lipid content, lipid-to-hydrotrope ratio), stabilizer concentration, pH and temperature of the buffer, as well as the temperature of the anhydrous mixture. The resulting nanoparticles were characterized by their mean particle size, polydispersity index, and zeta potential.
All nanoparticles obtained by systematically varying these parameters met the initial size (< 250 nm) and polydispersity index (< 0,3) criteria. The four most promising formulations, based on polydispersity index, were further evaluated for physical stability under room temperature storage weekly over one month. Formulations containing higher ethanol concentrations exhibited reduced stability, which was reflected in a decrease in zeta potential after four weeks.
Considering all results, the most optimal formulation was prepared at room temperature with phosphate buffer at pH 7,4, anhydrous mixture content of 10,0 %, a mass ratio of anhydrous mixture to stabilizer of 7 : 1, and a lipid-to-hydrotrope mass ratio of 2 : 1. This formulation exhibited the lowest initial polydispersity index, which remained unchanged over time, the zeta potential remained comparable, the preparation was reproducible, and the lipid content was high, which is important for drug loading. Moreover, the physiological pH of the dispersion (7,4) is favorable from the perspective of safety and reduced pain upon drug administration.
The »bottom-up« method proved to be robust and highly adaptable and can therefore be used in the future for the development of lyotropic liquid crystalline nanoparticles for the incorporation of various active pharmaceutical ingredients.
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