Effection of Lactic Acid Dissociation on Swelling-Based Short-Chain Fatty Acid Vesicles Nano-Delivery

Functionalized small-molecule assemblies can exhibit nano-delivery properties that significantly improve the bioavailability of bioactive molecules. This study explored the self-assembly of short-chain fatty acids (FA, Cn < 8) to form novel biomimetic nanovesicles as delivery systems. Lactic acid is involved in the regulation of multiple signaling pathways in cancer metabolism, and the dissociation of lactic acid (LA) is used to regulate the delivery effect of short-chain fatty acid vesicles. The study showed that the dissociation of lactic acid caused pH changes in the solution environment inducing hydrogen ion permeability leading to rapid osmotic expansion and shape transformation of FA vesicles. The intrinsic features of FA vesicle formation in the LA environment accompanied by hydrogen ion fluctuations, and the appearance of nearly spherical vesicles were investigated by transmission electron microscopy (TEM) and Fourier Transform Infrared Spectroscopy (FTIR). Compared with the vesicle membrane built by surfactants, the FA/LA composite system showed higher permeability and led to better membrane stability and rigidity. Finally, membrane potential studies with the IEC cell model demonstrate that lactate dissociation capacity can effectively increase the cellular adsorption of FA vesicles. Altogether, these results prove that FA vesicles can function as a stand-alone delivery system and also serve as potential development strategies for applications in a lactate environment.