Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems.

Controlling passive diffusion through an amphiphilic membrane is a key factor for the development of future smart generations of drug delivery systems. It also plays a crucial role in understanding fundamental biological systems through the design of new artificial cell models. We report herein a new concept of bolalipids designed as key components for the control of the membrane's permeability. Built on the scaffold of two natural phospholipids connected in the terminal fatty chain region through a polar linker, this specific bola pattern adopts two extreme conformations while self-assembling in water: a bent conformation, responsible for the curvature of the membrane, and an extended conformation, responsible for decreasing the membrane's fluidity. We also designed a bolalipid possessing an ester linker in the lipidic interface that enables stabilization of highly leaky DMPC SUV-liposomes. The nanoparticles were characterized by dynamic light scattering, cryogenic transmission electron microscopy, Fourier transform infrared, differential scanning calorimetry, fluorimetry, and coarse-grained molecular dynamics in order to validate this proof of concept.