Combined Liposomal Nanoparticles Based on Dihexadecyl Ester of (4-Aminobutanoyl)-L-Aspartic Acid and Its Pegylated Analogue for Drug Delivery

Abstract

ctive: Liposomes are one of the most promising systems for the delivery of biologically active substances (BAS) to target cells, particularly for crossing the blood–brain barrier in the treatment of central nervous system diseases. However, classical liposomes are rapidly taken up by cells of the reticuloendothelial system, which significantly limits their circulation time in the bloodstream. This study aimed to synthesize dihexadecyl ester of (4-aminobutanoyl)-L-aspartic acid and its pegylated analogue with MeO-PEG-2000 and to evaluate the physicochemical characteristics of the liposomal dispersions based on these compounds. Methods: Dihexadecyl ester of (4-aminobutanoyl)-L-aspartic acid and its MeO-PEG-2000 modified analogue were synthesized using stepwise condensation with dicyclohexylcarbodiimide and 4-dimethylaminopyridine, followed by chromatographic purification and structural characterization. Liposomal nanoparticles were prepared from the obtained lipids (and their mixtures) using thin-film hydration. Results and Discussion: The liposomal dispersions formed systems with mean hydrodynamic diameters of about 20–23 nm, which is optimal for functionalized transport systems. The pegylated liposomes exhibited a high ζ-potential and efficiently encapsulated hydrophilic biologically active substances, maintaining their size and charge during storage, which indicates high colloidal stability. Conclusions: The synthesized dihexadecyl ester of (4-aminobutanoyl)-L-aspartic acid and its MeO-PEG-2000 pegylated analogue form stable liposomal nanoparticles with high ζ-potential and high encapsulation efficiency for hydrophilic BAS. Pegylation significantly improves the colloidal stability of such liposomal systems and creates a promising platform for the development of long-circulating nanocarriers intended for drug delivery across biological barriers, including the blood–brain barrier.