Methicillin-resistant Staphylococcus aureus (MRSA) poses a case of highly resistant bacteria that warrants novel formulation interventions aiming for augmenting the antibiotics effects. Accordingly, Gelatinized core liposomes (GCL) were used to enhance the encapsulation and the antibacterial effect of the new natural hydrophilic antibiotic kojic acid (KA) in order to target the intra-monocyte MRSA infections. The antibacterial effect was evaluated using spectrophotometric micro-dilution against MRSA. The quantitative uptake of the formulations in monocytes was determined using the Histopaque separation. The formulations were also tested for cytotoxicity on monocytes using MTT assay. At last, treating intra-monocyte MRSA infection with gelatinized liposomes using 80 mg gelatin (GL-80) was performed.The GL-80 formulation significantly increased the entrapment efficiency (EE%) by 50% ± 2.2 with a mean size of 188.8 ± 11.5 nm. The GL-80 and conventional liposomes (CL) formulations showed an equal minimum inhibitory concentration (MIC) to the free KA on MRSA. However, the GL-80 showed a higher % uptake by monocytes with insignificant cytotoxicity. Moreover, a significant sustained reduction of the intracellular MRSA infecting monocytes was attained.The present work showed that KA loaded GCL is a promising platform in targeting the intra-monocyte MRSA infection of the inflamed tissues. Combating the antibiotic resistance was attained by enhancing the effect of a new natural antibiotic entity via a novel nano-carrier.