Delivery of novel vancomycin nanoplexes for combating methicillin resistant Staphylococcus aureus (MRSA) infections

Hassan, Daniel; Omolo, Calvin A.; Gannimani, Ramesh; Waddad, Ayman Y.; Mocktar, Chunderika; Rambharose, Sanjeev; Agrawal, Nikhil

doi:10.1016/j.ijpharm.2019.01.010

Cited by 34 publications

(15 citation statements)

References 66 publications

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“…Studies have shown that DFU usually presents polymicrobial infections; nevertheless, the most frequently identified organisms are Staphylococcus aureus , Staphylococcus epidermidis , coagulase-negative Staphylococcus spp., Enterococcus spp., Escherichia coli , Pseudomonas aeruginosa , Proteus mirabilis , and Klebsiella pneumoniae [ 6 ]. S. aureus , specially, methicillin-resistant S. aureus (MRSA), are opportunistic pathogens that can cause several types of infections from mild skin and soft-tissue infections to life-threatening endocarditis, such as, bacteremia, endocarditis, pneumonia, and bone and joint infections [ 7 ]. MRSA infections continue to be a major concern globally since these strains are usually resistant to several classes of antimicrobial drugs and often carry multiple virulence factors [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer

Silva

Peirone

Capita

et al. 2021

Biology

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Diabetic foot ulcers are a common cause of morbidity in diabetic patients. One of the main pathogens found in these ulcers is methicillin-resistant Staphylococcus aureus (MRSA). MRSA often carries resistance to several classes of antibiotics and their infections are becoming harder to treat. Therefore, new alternatives are urgently needed. Thus, this study aimed to investigate the capacity of topical ozonated oil application on the treatment of early-stage skin infected with MRSA in an animal model. Ozonated oil was prepared from a mixture of oils subjected to a gas stream of O2/O3 mixture. Sixteen Wistar rats were inoculated by an intradermic injection of MRSA suspension, producing an abscess lesion. After 3 days, the skin epidermis was removed to open the wound. Group 1 received an application of oil mixture without ozone treatment and Group 2 received an application of ozonated oil. After the treatment period, skin was collected, colony-forming units (CFU) of bacteria were quantified and the histological analysis of the skin was carried out. Skin samples from the control 1 and 2 had a bacterial load was of 1.1 × 105 and 5.7 × 103 CFU/mL, respectively. Group 2 showed better wound healing from mild to moderate epidermal regeneration. Topical application of ozonated vegetable oil in MRSA-infected skin in rats showed a small reduction of the bacterial load and better wound healing.

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Section: Introductionmentioning

confidence: 99%

Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer

Silva

Peirone

Capita

et al. 2021

Biology

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“…Several nanodrug delivery systems have been involved in the effective delivery of antimicrobials with great success, and currently, they are being been introduced into the market [ 9 , 10 ]. Lipidic vesicles are the most-employed nanostructures for drug delivery since their serendipitous discovery in 1964 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

et al. 2020

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Globally, human beings continue to be at high risk of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA); and current treatments are being depleted due to antimicrobial resistance. Therefore, the synthesis and formulation of novel materials is essential for combating antimicrobial resistance. The study aimed to synthesize a quaternary bicephalic surfactant (StBAclm) and thereof to formulate pH-responsive vancomycin (VCM)-loaded quatsomes to enhance the activity of the antibiotic against MRSA. The surfactant structure was confirmed using 1H, 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and high-resolution mass spectrometry (HRMS). The quatsomes were prepared using a sonication/dispersion method and were characterized using various in vitro, in vivo, and in silico techniques. The in vitro cell biocompatibility studies of the surfactant and pH-responsive vancomycin-loaded quatsomes (VCM-StBAclm-Qt1) revealed that they are biosafe. The prepared quatsomes had a mean hydrodynamic diameter (MHD), polydispersity index (PDI), and drug encapsulation efficiency (DEE) of 122.9 ± 3.78 nm, 0.169 ± 0.02 mV, and 52.22 ± 8.4%, respectively, with surface charge switching from negative to positive at pH 7.4 and pH 6.0, respectively. High-resolution transmission electron microscopy (HR-TEM) characterization of the quatsomes showed spherical vesicles with MHD similar to the one obtained from the zeta-sizer. The in vitro drug release of VCM from the quatsomes was faster at pH 6.0 compared to pH 7.4. The minimum inhibitory concentration (MIC) of the drug loaded quatsomes against MRSA was 32-fold and 8-fold lower at pH 6.0 and pH 7.4, respectively, compared to bare VCM, demonstrating the pH-responsiveness of the quatsomes and the enhanced activity of VCM at acidic pH. The drug-loaded quatsomes demonstrated higher electrical conductivity and a decrease in protein and deoxyribonucleic acid (DNA) concentrations as compared to the bare drug. This confirmed greater MRSA membrane damage, compared to treatment with bare VCM. The flow cytometry study showed that the drug-loaded quatsomes had a similar bactericidal killing effect on MRSA despite a lower (8-fold) VCM concentration when compared to the bare VCM. Fluorescence microscopy revealed the ability of the drug-loaded quatsomes to eradicate MRSA biofilms. The in vivo studies in a skin infection mice model showed that groups treated with VCM-loaded quatsomes had a 13-fold decrease in MRSA CFUs when compared to the bare VCM treated groups. This study confirmed the potential of pH-responsive VCM-StBAclm quatsomes as an effective delivery system for targeted delivery and for enhancing the activity of antibiotics.

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“…S. aureus strains isolated from humans, pigs, and cattle have created intermediate resistance to vancomycin [ 92 ]. Vancomycin formulated as nanoplexes of the antibiotic with dextran sulfate sodium salt has recently addressed MRSA infections; the size, polydispersity, and zeta potential of the optimized nanoplexes were 84.6 ± 4.3 nm, 0.449 ± 0.024, and −33.0 ± 4.9 mV, respectively, with 90.4 ± 0.8% complexation efficiency and 62.3 ± 0.2% drug loading; in vivo studies using a BALB/c mouse skin infection model revealed that nanoplexes reduced MRSA burden by 2.3−fold compared to bare vancomycin [ 93 ]. Liposomal vancomycin topical formulations have also produced similar results against MRSA, reconfirming the importance of the formulation for fighting drug−resistant microbia [ 94 ].…”

Section: Asa With Ampsmentioning

confidence: 99%

Antimicrobial Polymer−Based Assemblies: A Review

Carmona-Ribeiro

Araújo

2021

IJMS

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An antimicrobial supramolecular assembly (ASA) is conspicuous in biomedical applications. Among the alternatives to overcome microbial resistance to antibiotics and drugs, ASAs, including antimicrobial peptides (AMPs) and polymers (APs), provide formulations with optimal antimicrobial activity and acceptable toxicity. AMPs and APs have been delivered by a variety of carriers such as nanoparticles, coatings, multilayers, hydrogels, liposomes, nanodisks, lyotropic lipid phases, nanostructured lipid carriers, etc. They have similar mechanisms of action involving adsorption to the cell wall, penetration across the cell membrane, and microbe lysis. APs, however, offer the advantage of cheap synthetic procedures, chemical stability, and improved adsorption (due to multipoint attachment to microbes), as compared to the expensive synthetic routes, poor yield, and subpar in vivo stability seen in AMPs. We review recent advances in polymer−based antimicrobial assemblies involving AMPs and APs.

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Delivery of novel vancomycin nanoplexes for combating methicillin resistant Staphylococcus aureus (MRSA) infections

Cited by 34 publications

References 66 publications

Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer

Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

Antimicrobial Polymer−Based Assemblies: A Review

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