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. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained
release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery.
Objective: In order to improve the oral bioavailability of rifaximin and expand the clinical application
of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles
(RFX-SLNs).
Methods: This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods
and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, 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 water (3% PVA) and oil
(myristic acid) ratio of 1:19. RFX-SLNs were spherical in 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. This indicates
that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX,
RFX-SLNs showed 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. This not only
opens up avenues for the clinical application of RFX but also provides a way for the development of
new dosage forms of water-soluble drugs and the expansion of their clinical application scope.
Huang Rong,Cai Guang-Qing,Li Jian,Li Xi-Sheng,Liu Hai-Ting,Shang Xue-Ling,Zhou Jian-Dang,Nie Xin-Min,Gui Rong
Background Due to the intelligent survival strategy and self-preservation of methicillin-resistant Staphylococcus aureus (MRSA), many antibiotics are ineffective in treating MRSA infections. Nano-drug delivery systems have emerged as a new method to overcome this barrier. The aim of this study was to construct a novel nano-drug delivery system for the treatment of MRSA infection, and to evaluate the therapeutic effect and biotoxicity of this system. We prepared a nano silver metal-organic framework using 2-methylimidazole as ligand and silver nitrate as ion provider. Vancomycin (Vanc) was loaded with Ag-MOF, and nano-sized platelet vesicles were prepared to encapsulate Ag-MOF-Vanc, thus forming the novel platelet membrane-camouflaged nanoparticles PLT@Ag-MOF-Vanc.Results The synthesized Ag-MOF particles had uniform size and shape of radiating corona. The mean nanoparticle size and zeta potential of PLT@Ag-MOF-Vanc were 148 nm and − 25.6 mV, respectively. The encapsulation efficiency (EE) and loading efficiency (LE) of vancomycin were 81.0 and 64.7 %, respectively. PLT@Ag-MOF-Vanc was shown to be a pH-responsive nano-drug delivery system with good biocompatibility. Ag-MOF had a good inhibitory effect on the growth of three common clinical strains (Escherichia coli, Pseudomonas aeruginosa, and S. aureus). PLT@Ag-MOF-Vanc showed better antibacterial activity against common clinical strains in vitro than free vancomycin. PLT@Ag-MOF-Vanc killed MRSA through multiple approaches, including interfering with the metabolism of bacteria, catalyzing reactive oxygen species production, destroying the integrity of cell membrane, and inhibiting biofilm formation. Due to the encapsulation of the platelet membrane, PLT@Ag-MOF-Vanc can bind to the surface of the MRSA bacteria and the sites of MRSA infection. PLT@Ag-MOF-Vanc had a good anti-infective effect in mouse MRSA pneumonia model, which was significantly superior to free vancomycin, and has no obvious toxicity.Conclusion sPLT@Ag-MOF-Vanc is a novel effective targeted drug delivery system, which is expected to be used safely in anti-infective therapy of MRSA.Graphic abstract
危险品化学品经营许可证（带存储）