Tripolar\nBolalipids as Key Components of Sustained-Release\nDrug Delivery Systems

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