Morphological transformation of self-assembled nanostructures prepared from cholesteryl acyl didanosine and the optimal formulation of nanoparticulate systems: Effects of solvents, acyl chain length and poloxamer 188

Self-assembled nanostructures were obtained through injecting cholesteryl-succinyl didanosine (CSD) solutions in tetrahydrofuran (THF) into water. The incorporation of THF leads to CSD flexible bilayers. Spherical vesicles of CSD initially formed based on hydrophobic interaction and transformed to short nanotubes with THF leaving. A large proportion of THF led to formation of long flexible nanoribbons, also transforming to short nanotubes after removing THF because of rigid bilayers recovering. Cholesteryl-adipoyl didanosine (CAD) only formed spherical vesicles due to its long and flexible tails. A triblock copolymer, poloxamer 188 (P188) could insert into CSD monolayers at the air/water interface. P188 stabilized CSD nanoparticulate systems by incorporation and adsorption. The optimal formulation of nanoparticulate systems was identified and the appropriate ratio of CSD/P188 and CSD concentration in injected solutions were the keys. A highly concentrated system had a narrow size distribution, allowing heat sterilization at 100 °C, and resisting aggregation under high gravity accelerations in spite of the low zeta potential of −18.5 mV. A gel–liquid crystalline phase transition at 47 °C occurred. The system may become promising self-assembled drug delivery systems (SADDS) for anti-HIV therapy.

Graphical abstractSpherical vesicles are formed by injecting cholesteryl-succinyl didanosine solutions in THF into water. THF in bilayers improves spherical vesicles to fuse to long flexible nanoribbons further transforming to short nanotubes.Figure optionsDownload full-size imageDownload as PowerPoint slide