Solid Lipid Nanoparticles Based on Monosubstituted Pillar[5]arenes: Chemoselective Synthesis of Macrocycles and Their Supramolecular Self-Assembly

Abstract

Novel monosubstituted pillar[5]arenes with one or two terminal carboxyl groups were synthesized by the reaction of succinic anhydride with pillar[5]arene derivative containing a diethylenetriamine function. The ability for non-covalent self-assembly in chloroform, dimethyl sulfoxide, as well as in tetrahydrofuran-water system was studied. The ability of the synthesized macrocycles to form different types of associates depending on the substituent nature was established. The formation of stable particles with average diameter of 192 nm in chloroform and of 439 nm in DMSO was shown for pillar[5]arene containing two carboxyl fragments. Solid lipid nanoparticles (SLN) based on monosubstituted pillar[5]arenes were synthesized by nanoprecipitation in THF-water system. Minor changes in the structure of the macrocycle substituent can dramatically influence the stability and shape of SLN (spherical and rod-like structures) accordingly to DLS and TEM. The presence of two carboxyl groups in the macrocycle substituent leads to the formation of stable spherical SLN with an average hydrodynamic diameter of 364–454 nm. Rod-like structures are formed by pillar[5]arene containing one carboxyl fragment, which diameter is about of 50–80 nm and length of 700–1000 nm. The synthesized stable SLN open up great prospects for their use as drug storage systems.