The study shows that the antimicrobial peptide LL‑37 can slip into lung surfactant quickly, but it gets stuck to the surfactant’s charged head groups, which neutralizes its ability to kill bacteria. Adding tiny particles made of sodium cholate protects the peptide, letting it move through the surfactant without losing its charge and without damaging the surfactant itself. This suggests a way to deliver LL‑37 (and similar peptides) to the lungs more effectively.

Molecular dynamics simulations were successfully performed to understand the absorption mechanism of antimicrobial peptides LL-37, CATH-2, and SMAP-29 in a lung surfactant model. The antimicrobial peptides quickly penetrate in the lung surfactant model in dozens or hundreds nanoseconds, but they electrostatically interact with the lipid polar heads during the simulation time of 2 μs. This electrostatic interaction should be the explanation for the inactivation of the antimicrobial peptides when co-administrated with lung surfactant. As they strongly interact with the lipid polar heads of the lung surfactant, there is no positive charge available on the antimicrobial peptide to attack the negatively charged bacteria membrane. In order to avoid the interaction of peptides with the lipid polar heads, sodium cholate was used to form nanoparticles which act as an absorption enhancer of all antimicrobial peptides used in this investigation. The nanoparticles of 150 molecules of sodium cholate with one peptide were inserted on the top of the lung surfactant model. The nanoparticles penetrated into the lung surfactant model, spreading the sodium cholate molecules around the lipid polar heads. The sodium cholate molecules seem to protect the peptides from the interaction with the lipid polar heads, leaving them free to be delivered to the water phase. The penetration of peptides alone or even the peptide nanoparticles with sodium cholate do not collapse the lung surfactant model, indicating to be a promisor drug delivery system to the lung. The implications of this finding are that antimicrobial peptides may only be co-administered with an absorption enhancer such as sodium cholate into lung surfactant in order to avoid inactivation of their antimicrobial activity.