scholarly journals Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 321
Author(s):  
Magda Ferreira ◽  
Sandra N. Pinto ◽  
Frederico Aires-da-Silva ◽  
Ana Bettencourt ◽  
Sandra I. Aguiar ◽  
...  

Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.

1980 ◽  
Vol 6 (suppl A) ◽  
pp. 55-61 ◽  
Author(s):  
J. Klastersky ◽  
H. Gaya ◽  
S. H. Zinner ◽  
C. Bernard ◽  
J-C. Ryff ◽  
...  

Author(s):  
Djameh, Georgina I. ◽  
Nyarko, Samuel ◽  
Tetteh-Tsifoanya, Mark ◽  
Marfo, Frances M. ◽  
Adjei, Samuel ◽  
...  

Snakebite envenomation is a major health concern in developing countries causing significant mortality and morbidity. With over 1.2 million cases annually caused by medically important snake species belonging to the two families Viperidae (Echis spp. and Bitis spp.) and Elapidae (Naja spp. and Dendroaspis spp.). Several antivenoms are being produced and distributed to western sub-Saharan Africa for treatment of envenomation with the absence of preclinical efficacy studies. The present study evaluated the preclinical efficacy of venoms from Echis leucogaster, Echis ocellatus, Bitis arietans, Bitis gabonica, Naja haje, Naja melanoleuca, Naja nigricollis, Dendroaspis jamesoni, Dendroaspis polylepis and Dendroaspis viridis against a polyvalent Snake Venom Antiserum - African IHS (lyophilised), manufactured by VINS Bioproducts Limited (Telangana, India). Our in vitro results showed that, the SVA- AIHS contains antibodies that are capable of recognizing and binding majority of protein components representative of all eight major protein families of venoms of the snake species tested by double immunodiffusion assay and confirmed by western blot. The venom antiserum exhibited high neutralization efficacy against all the viperid and elapid snake species venoms in in vivo studies and confirmed the manufacturer’s recommended neutralization capacity. This is clear evidence that the VINS polyvalent SVA-AIHS batch tested has strong neutralizing capacity and will be useful in treating envenoming by most African viperid and some elapid snake species.


2015 ◽  
Vol 82 (1) ◽  
pp. 394-401 ◽  
Author(s):  
Jakub Kwiecinski ◽  
Manli Na ◽  
Anders Jarneborn ◽  
Gunnar Jacobsson ◽  
Marijke Peetermans ◽  
...  

ABSTRACTStaphylococcus aureusbiofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role inS. aureusbiofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating onS. aureusbiofilm formation was tested within vitromicroplate biofilm assays and anin vivomouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by variousS. aureusstrains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics.In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduceS. aureusbiofilm formation bothin vitroandin vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.


Author(s):  
Cong Yao ◽  
Meisong Zhu ◽  
Xiuguo Han ◽  
Qiang Xu ◽  
Min Dai ◽  
...  

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.


1996 ◽  
Vol 40 (10) ◽  
pp. 2258-2261 ◽  
Author(s):  
S Schwank ◽  
J Blaser

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.


2015 ◽  
Vol 99 (9) ◽  
pp. 4031-4043 ◽  
Author(s):  
Mariusz Grinholc ◽  
Joanna Nakonieczna ◽  
Grzegorz Fila ◽  
Aleksandra Taraszkiewicz ◽  
Anna Kawiak ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2821
Author(s):  
Norul Ashikin Norzain ◽  
Zhi-Wei Yu ◽  
Wei-Chih Lin ◽  
Hsing-Hao Su

This paper describes the fabrication of a structural scaffold consisting of both randomly oriented nanofibers and triangular prism patterns on the scaffold surface using a combination technique of electrospinning and collector templates. The polycaprolactone (PCL) nanofibers were electrospun over a triangular prism pattern mold, which acted as a template. The deposited scaffold was removed from the template to produce a standalone structural scaffold of three-dimensional micropatterned nanofibers. The fabricated structural scaffold was compared with flat randomly oriented nanofibers based on in vitro and in vivo studies. The in vitro study indicated that the structural scaffold demonstrated higher fibroblast cell proliferation, cell elongation with a 13.48 ± 2.73 aspect ratio and 70% fibroblast cell orientation compared with flat random nanofibers. Among the treatment groups, the structural scaffold escalated the wound closure to 92.17% on day 14. Histological staining of the healed wound area demonstrated that the structural scaffold exhibited advanced epithelization of the epidermal layer accompanied by mild inflammation. The proliferated fibroblast cells and collagen fibers in the structural scaffold appeared denser and arranged more horizontally. These results determined the potential of micropatterned scaffolds for stimulating cell behavior and their application for wound healing.


2019 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Marvit Osman Widdat Allah ◽  
Ayat Ahmed Alrasheid ◽  
Eltayeb Suliman Elamin

Diabetes mellitus in Sudan is one of public health concern since it causes significant mortality and complications for long term. Though conventional drugs are used in the management of diabetes mellitus they are expensive, unavailable and also have numerous side effects. Khaya senegalensis has traditionally used in the management of diabetes. The present study was conducted to examine the In vitro and In vivo anti-diabetic activity of leaves and bark extracts of Khaya senegalensis. The leaves and bark of the plant were extracted with ethanol 96%, and then tested for anti-diabetic activity in a series of in vitro models and a type 2 diabetes model of rats. In vitro bark extract of k.senegalensis showed higher inhibitory activities against the enzyme with IC50 value 226.14 µg/ml. In vivo oral administration of the extracts of the k. senegalensis exhibited decrease in blood sugar level and was found to be time dependent. Bark extract showed strong in vitro and in vivo anti diabetic activity.  


2021 ◽  
Author(s):  
Jessica Bratt

<p>The spread of antibiotic resistance and the emergence of multi-drug resistant bacteria is a major threat to public health. This study investigated a unique cytosine rich DNA structure, the i-Motif to deliver soluble Ag+ as a novel antimicrobial agent (AgiMs). AgiMs were evaluated in vitro against P. aeruginosa and A. baumannii strains. AgiMs displayed significant antibacterial activity against both P. aeruginosa and A. baumannii (median MIC: 0.875 µM and 0.75 µM, respectively) by rapid, bactericidal and concentration-dependent effect. Low concentrations of AgiMs showed efficacy against PAO1 20-h biofilms, resulting in 57% reduction in biomass (5 x MIC). A single dose of AgiMs extended survival of G. Mellonella larvae, with the therapeutic benefit paralleled in the reduction of internal bacterial load. Synergistic interactions were observed with the combination of AgiMs and tobramycin, a common antibiotic used to treat P. aeruginosa infections; indicating the potential for AgiMs to reinstate the potency of current antibiotics. This silver-based agent might be an alternative to the failing antibiotic regimes for MDR resistant infections. Further in vitro and in vivo studies are warranted to confirm the therapeutic potential. </p>


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