Intermolecular Dynamics of Monoglyceride Mesophases with Their Biomacromolecular Corona

Advances in the development of lipid nanoparticles have resulted in delivery systems that both protect the encapsulated drug and improve therapeutic outcomes. When introduced in vivo, nanoparticles are rapidly covered by a biomolecular corona, influencing their biological fate, i.e., interaction with cells, uptake, and intracellular fate. This study explores the interactions between nonlamellar lipidic drug delivery systems and non-lipolytic components of complex cell culture media, focusing on the dynamic formation of the corona and its effects on the lipid nanoparticle behavior. Monoglyceride formulations were monitored for changes in nanostructure and particle size, and mechanisms for these changes were elucidated. Not only do these biomacromolecules influence the size and structure of the nanoparticles themselves, but they can simultaneously diffuse into the mesophase nanostructure. The study highlights that lipid nanoparticles undergo dynamic changes in physiological conditions influenced by adsorbed proteins and other nondegradative components in complex cell culture media, separate from effects caused by lipases or other enzymatic factors. These induced structural transformations can significantly alter the nanoparticles' physical properties and drug release profiles, potentially causing deviation from their intended therapeutic performance. Understanding these interactions is thus crucial for optimizing the design and functionality of lipid-based drug delivery systems in biomedical applications.