Levofloxacin-loaded surfactant nanocarriers: a computational study.

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Drug Delivery

Background:

• Levofloxacin is a widely used fluoroquinolone antibiotic.
• Micelles, such as sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB), are crucial in drug formulation.
• Understanding drug-micelle interactions is key to optimizing drug delivery systems.

Purpose of the Study:

• To investigate the interaction dynamics and orientation of levofloxacin with anionic (SDS) and cationic (CTAB) micelles.
• To determine the encapsulation efficiency and binding affinity of levofloxacin for both micelle types.
• To elucidate the molecular mechanisms governing levofloxacin-micelle interactions.

Main Methods:

• Extensive all-atom molecular dynamics simulations were employed.
• Drug/micelle ratios, including loading capacity and entrapment efficiency, were estimated.
• Relative binding energies and molecular orientations were calculated.

Main Results:

• Levofloxacin exhibited significantly higher encapsulation efficiency in SDS micelles (∼80%) compared to CTAB micelles (∼8%).
• Simulations showed tilted orientations for levofloxacin in both micelle types, with specific interactions of charged groups (piperazine and carboxylic acid) with micelle headgroups.
• Levofloxacin demonstrated stronger binding to SDS micelles than CTAB micelles, supported by binding energy calculations.
• Concerted columnar stacks of levofloxacin were observed in both micelle types, driven by π-π interactions and hydrogen bonding.

Conclusions:

• Levofloxacin preferentially interacts with and is more efficiently encapsulated by anionic SDS micelles.
• The charged nature of levofloxacin's functional groups and their interactions with micelle headgroups dictate binding affinity and orientation.
• Molecular dynamics simulations provide valuable insights into the behavior of fluoroquinolone antibiotics within micellar systems, relevant for drug formulation.