Liquid crystalline nanoparticles are thermodynamically stable particles that combine the properties of liquid crystals and nanocarriers. Their dispersions, called cubosomes or hexosomes, are formed by the self-assembly of amphiphilic lipids or mesogens in an aqueous medium. They represent a unique nanodelivery system for incorporation of active pharmaceutical ingredients of varying polarities, enabling their protection from degradation and sustained release, as well as cost-effective production, are biocompatible, biodegradable and non-toxic.
The aim of this master's thesis was to optimize the formulation of liquid crystalline nanoparticles for the encapsulation of peptide drug thymosin alpha 1. Nanoparticles based on glyceryl monooleate (lipid and mesogen), poloxamer 407 (steric stabilizer) and ethanol (hydrotropic agent) were prepared using low-energy »bottom-up« methods and high-energy »top-down« methods. In preliminary studies we systematically evaluated the influence of formulation composition and aqueous medium on the formation and properties of the nanoparticles. A homogeneous, milky-white dispersion free of aggregates formed in formulations with a lipid:stabilizer ratio of 10:1, lipid:ethanol 2:1 or lipid:stabilizer 7,7:1, lipid:ethanol 1:1, prepared using a »bottom-up« approach. A phosphate buffer with a pH of 7,4 proved to be the optimal aqueous medium and a 1 % addition of polysorbate 80 also contributed to achieving the desired properties of the dispersions. In the case of »top-down« preparation, a homogeneous dispersion was obtained with a lipid:stabilizer ratio of 9:1.
We incorporated the peptide into three optimal formulations that maintained physical stability after 28 days and evaluated the encapsulation efficiency using dialysis, ultracentrifugation and ultrafiltration. The first two methods were not suitable as the measured concentrations of the incorporated peptide were below the limit of quantification (0,5 mg/L), by the ultrafiltration, however, we determined an encapsulation efficiency of 61,8 %.
Through experiments, we have demonstrated that the two most commonly used methods for preparing liquid crystalline nanoparticles are suitable for incorporating a peptide active ingredient and for preparing stable dispersions. The results described provide a solid foundation for further investigation and optimization of liquid crystalline nanoparticles.
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