Development Of Sustained Release SLNS For Synergistic Co-Delivery Of Ofloxacin And Meropenem Against MDR Bacteria

Multidrug-resistant (MDR) bacterial infection is epidemiologically alarming and an important issue that requires innovative, highly effective drug delivery methods in contemporary healthcare. This paper is devoted to the design of a sustained released solid lipid nanoparticle (SLN) system, which is used to co-deliver two powerful antibiotics, Ofloxacin, and Meropenem, in a synergism manner. To produce the SLNs, hot homogenization and ultrasonication methods were used with the utilization of biocompatible lipids and surfactants to facilitate the best entrapment and drug discharge. Characterization of the formulation was done with respect to particle size, zeta potential, polydispersity index (PDI), entrapment efficiency and the drug loading which fell considerably within the desirable range. The compatible combination of drug and its stable integration into the lipid matrix was revealed by spectroscopic (FTIR) and thermal (DSC) analysis. In vitro drug release results had a biphasic pattern and release was sustained beyond 24 hours and conforming to KorsmeyerPeppas and Higuchi meters. The antibacterial evaluation was carried out under the agar well diffusion technique, which revealed better inhibition zones against all E. coli, S. aureus, K. Pneumoniae, and P. aeruginosa using SLN antibacterial compared to free drugs. ICH Q1A(R2) stability testing conditions showed excellent physical and chemical stability at three month conditions. The release and activity consistency were further confirmed by Principal Component Analysis (PCA) and ANOVA. These findings indicate that co-delivery by SLN is a potentially excellent strategy that allows improving the therapeutic efficiency of Ofloxacin and Meropenem, due to prolonged release and lower dosing interval, patient compliance, and potentially resulting in the reduction of antibiotic resistance development. The work provides the foundation of future in vivo research and clinical application of SLN-based co-delivery systems as an anti-infective agent to treat MDR bacterial infections.