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.