Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.

Abstract

Introduction/background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption.

Objective: In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed a RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs).

Methods: This study first screened the formula of RFX-SLNs through single factor screening. After that, the particle size, zeta potential and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model.

Results: The optimal formulation of RFX-SLNs was 1% RFX with a water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. RFX-SLNs showed a good therapeutic effects in a mouse MRSA pneumonia infection model.

Conclusion: This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs.