The
lipid dynamics and phase play decisive roles in drug encapsulation
and delivery to the intracellular target. Thus, understanding the
dynamic and structural alterations of membranes induced by drugs is
essential for targeted delivery. To this end, united-atom molecular
dynamics simulations of a model bilayer, dioctadecyldimethylammonium
bromide (DODAB), are performed in the absence and presence of the
usual nonsteroidal anti-inflammatory drug (NSAID), aspirin, at 298,
310, and 345 K. At 298 and 310 K, the bilayers are in the interdigitated
two-dimensional square phases, which become rugged in the presence
of aspirin, as evident from height fluctuations. At 345 K, the bilayer
is in the fluid phase in both the absence and presence of aspirin.
Aspirin is preferentially located near the oppositely charged headgroup
and creates void space, which leads to an increase in the interdigitation
and order parameters. Although the center of mass of lipids experiences
structural arrest, they reach the diffusive regime faster and have
higher lateral diffusion constants in the presence of aspirin. Results
are found to be consistent with recent quasi-elastic neutron scattering
studies that reveal that aspirin acts as a plasticizer and enhances
lateral diffusion of lipids in both ordered and fluid phases. Different
relaxation time scales of the bonds along the alkyl tails of DODAB
due to the multitude of lipid motions become faster upon the addition
of aspirin. Our results show that aspirin insertion is most favorable
at physiological temperature. Thus, the ordered, more stable, and
faster DODAB bilayer can be a potential drug carrier for the protected
encapsulation of aspirin, followed by targeted and controlled drug
release with antibacterial activity in the future.