Targeting Acne: Development of Monensin-Loaded Nanostructured Lipid Carriers.

PURPOSE: The emergence of antimicrobial resistance (AMR) has made treating acne vulgaris increasingly challenging, thus underscoring the urgent need for new antibacterial therapies. This research aimed to discover, for the first time, the efficacy of monensin (MON) against acne pathogens by encapsulating MON in nanostructured lipid carriers (NLCs) to achieve targeted topical delivery.

METHODS

MON-loaded NLCs were formulated and optimized using the Design of Experiments (DoE) approach and incorporated in a gel formulation. The potential of MON, MON-NLCs, and its gel formulation was investigated against resistant human isolates of C. acnes, Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) using the agar dilution method. Using the porcine ear skin, the ex vivo deposition of MON was evaluated in different skin layers. The cytotoxicity assay was also performed at antibacterial concentrations using the keratinocyte cell line.

RESULTS

MON-loaded NLCs were developed using stearic acid, oleic acid, and Tween® 80 and optimized with particle size, polydispersity index, and zeta potential of 96.65 ± 0.94 nm, 0.13 ± 0.01, and -36.50 ± 0.30 mV, respectively. The ex vivo deposition experiments showed that MON did not penetrate any skin layer using its water dispersion. However, a significant amount of MON was deposited into the epidermal layer using MON-NLC (4219.86 ± 388.32 ng/cm²) and gel formulation (8180.73 ± 482.37 ng/cm²), whereas no MON permeated to the dermis layer using gel formulation. The antibacterial study revealed the potential of MON, MON-NLC, and gel formulation against C. acnes isolates (MIC range 0.125-4 µg/mL, 0.25-4 µg/mL, and 0.125-1 µg/mL respectively). The cell viability results suggested MON-NLC formulation as a safe topical treatment effective at antibacterial concentrations.

CONCLUSION

This research highlights the novel ability of MON against resistant acne-causing pathogens and the potential of MON-NLCs to deliver MON to the targeted epidermal skin layer effectively.