Overcoming MRSA Antibiotic Resistance Through Losartan Repurposing with Carbon Dot-Conjugated Cerosomal Nanocarriers.

Background/

Objectives

Methicillin-resistant Staphylococcus aureus (MRSA) presents a serious hurdle in combating antibiotic-resistant skin infections. This study aimed to repurpose losartan potassium (LOS) through its incorporation into cerosomal nanocarriers (CERs) and further functionalization with carbon dots (CDs) to enhance antibacterial efficacy.

Methods

LOS-CERs were fabricated by the thin-film hydration method and further optimized using a D-optimal mixture design.

Results

The optimized CERs, composed of phytantriol (20 mg), ceramide (30 mg), and CTAB (20 mg), exhibited high entrapment efficiency (97.07 ± 0.07%), a nanoscale particle size (372.50 ± 0.50 nm), and a positive zeta potential (+33.24 ± 0.04 mV). FT-IR analysis confirmed successful conjugation of CDs to CERs through surface functional interactions. Ex vivo permeation and confocal microscopy studies demonstrated that the CD-CER formulation sustained LOS release and enhanced its deposition within skin layers compared with the LOS solution. Using a murine model of MRSA USA300-induced skin infection, the CD-CER formulation achieved superior antibacterial efficacy, reducing the bacterial load by 3.85 log10 CFU relative to the untreated control, compared with a 3.04 log10 CFU reduction for the LOS solution. Histological evaluation supported improved healing in CD-CER-treated groups.

Conclusions

Overall, CD-functionalized CERs offer a promising multifunctional nanoplatform for repurposing LOS as a topical therapeutic against MRSA-associated skin infections.