Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA)

Rani, Nur Najihah Izzati Mat; Chen, Xiang Yi; Alzubaidi, Zahraa M.; Azhari, H. Nour; Khaithir, Tzar Mohd Nizam; Buang, Fhataheya; Tan, Geok Chin; Wong, Yin Ping; Said, Mazlina Mohd; Hamid, Azmy A.; Amin, Mohd Cairul Iqbal Mohd

doi:10.1016/j.ajps.2021.11.004

Cited by 19 publications

(10 citation statements)

References 84 publications

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“…Researchers have also explored liposomal formulations of different antibiotics. For instance, Rani et al (2022) have designed liposomes co-loading VCM and daptomycin, with an external surface mimicking the red blood cells membrane [ 62 ]. The authors only evaluated the antibacterial activity against planktonic bacteria, while our study also presents biofilm results.…”

Section: Resultsmentioning

confidence: 99%

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

Pinho,

Ferreira,

Coelho

et al. 2024

Pharmaceuticals

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Methicillin-resistant Staphylococcus aureus (M RSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhance the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with similar potency between tested formulations. In MRSA-C1, minimal inhibitory concentrations (MIC) for Free RFB and liposomal RFB were 0.009 and 0.013 μg/mL, respectively. Minimum biofilm inhibitory concentrations able to inhibit 50% biofilm growth (MBIC50) for Free RFB and liposomal RFB against MRSA-C1 were 0.012 and 0.008 μg/mL, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. The in vivo results demonstrated a significant reduction in bacterial burden and growth index in major organs of mice treated with RFB formulations, as compared to Control and VCM (positive control) groups. Furthermore, the VCM therapeutic dose was two fold higher than the one used for RFB formulations, reinforcing the therapeutic potency of the proposed strategy. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

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Section: Resultsmentioning

confidence: 99%

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

Pinho,

Ferreira,

Coelho

et al. 2024

Pharmaceuticals

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“…In fact, in two studies concerning daptomycin liposomes reported before, targeted liposomes were considered, in which Dapto was conjugated with PEG and attached on a liposome surface to assist their targeting to bacteria and also loaded alone or with another drug in the liposomes [ 44 , 45 ]. In the earlier study, such Dapto liposomes demonstrated specific binding to MRSA using flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…In comparison to free drugs, the formulations sustained the release of drugs for 3 days and evaded detection by macrophages. Additionally, the targeted liposomes reduced the MIC and significantly increased bacterial permeability (compared to the free drug), resulting in more than 80% bacterial death within 4 h [ 45 ]. Other previous studies involving Dapto liposomes included (i) proliposomes that were prepared for oral delivery and were found to realize a significant increase in oral bioavailability of Dapto [ 24 ]; (ii) flexible Dapto-liposomes that were found to enhance the ability of Dapto to permeate the skin and demonstrate antibacterial activity against biofilms [ 25 ]; (iii) liposomes for the co-delivery of Dapto with clarithromycin that were demonstrated to produced significant anti-MRSA activity in the presence of only one-thirtieth of the concentration required when only Dapto-liposomes were used [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Daptomycin Liposomes Exhibit Enhanced Activity against Staphylococci Biofilms Compared to Free Drug

Gkartziou,

Plota,

Kypraiou

et al. 2024

Pharmaceutics

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The purpose of the present study was to investigate the anti-staphylococcal activity of liposomal daptomycin against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin-resistant. Neutral and negatively charged daptomycin-loaded liposomes were prepared using three methods, namely, thin-film hydration (TFH), a dehydration–rehydration vesicle (DRV) method, and microfluidic mixing (MM); moreover, they were characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release, and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30–35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserved its bioactivity. Biofilm mass (crystal violet, CV), biofilm viability (MTT), and growth curve (GC) assays evaluated the antimicrobial activity of neutral and negatively charged daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacterial growth (compared to the free drug) for all species studied, while negatively charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as the matured biofilms of low daptomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) strains were almost completely eradicated by liposomal-daptomycin, indicating the need for their further exploration as antimicrobial therapeutics.

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“…In this line, liposomes conjugated with mannose (ligand) have provided higher uptake into the biofilm matrix of S. aureus [ 213 ]. In a very recent work, Rani et al showed the potential of targeted delivery of drug-loaded liposomes coated with a red blood cell membrane against MRSA [ 214 ]. The authors used a targeting ligand that enables the binding of the liposomes to the cell wall of S. aureus and the formulation reduced the MIC and evaded macrophage uptake.…”

Section: Nanotechnology-based Approaches To Target Staphylo...mentioning

confidence: 99%

Regulation of Staphylococcus aureus Virulence and Application of Nanotherapeutics to Eradicate S. aureus Infection

Kannappan

Poonguzhali²,

Shi

et al. 2023

Pharmaceutics

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Staphylococcus aureus is a versatile pathogen known to cause hospital- and community-acquired, foodborne, and zoonotic infections. The clinical infections by S. aureus cause an increase in morbidity and mortality rates and treatment costs, aggravated by the emergence of drug-resistant strains. As a multi-faceted pathogen, it is imperative to consolidate the knowledge on its pathogenesis, including the mechanisms of virulence regulation, development of antimicrobial resistance, and biofilm formation, to make it amenable to different treatment strategies. Nanomaterials provide a suitable platform to address this challenge, with the potential to control intracellular parasitism and multidrug resistance where conventional therapies show limited efficacy. In a nutshell, the first part of this review focuses on the impact of S. aureus on human health and the role of virulence factors and biofilms during pathogenesis. The second part discusses the large diversity of nanoparticles and their applications in controlling S. aureus infections, including combination with antibiotics and phytochemicals and the incorporation of antimicrobial coatings for biomaterials. Finally, the limitations and prospects using nanomaterials are highlighted, aiming to foster the development of novel nanotechnology-driven therapies against multidrug-resistant S. aureus.

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Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA)

Cited by 19 publications

References 84 publications

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

Daptomycin Liposomes Exhibit Enhanced Activity against Staphylococci Biofilms Compared to Free Drug

Regulation of Staphylococcus aureus Virulence and Application of Nanotherapeutics to Eradicate S. aureus Infection

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