A novel combination therapy for multidrug resistant pathogens using chitosan nanoparticles loaded with β-lactam antibiotics and β-lactamase inhibitors

Author(s):  
Peixin Fan ◽  
Zhengxin Ma ◽  
Arianna J. Partow ◽  
Miju Kim ◽  
Grace M. Shoemaker ◽  
...  
2021 ◽  
Author(s):  
Tohid Piri Gharaghie ◽  
Sheida Beiranvand ◽  
Neda Jegargoshe Shirin ◽  
Yalda Elahianfar ◽  
Somayeh Ghahari ◽  
...  

Abstract In the present study, the antibacterial and antibiofilm effects of Thymol-based chitosan nanogels were investigated. After clinical screening of MDR strains from the hospital environment, the morphological characteristics of the synthesized nanoparticles were identified using SEM, DLS, XRD and FTIR and the efficiency of encapsulation, stability and drug release were evaluated. The expression of OmpA and PgaB biofilm genes were determined by q-Real-Time PCR and the antibacterial and cytotoxic properties of the nanoparticles were determined by well diffusion and MTT methods, respectively. Nanoparticles with a size of 82.71 nm, encapsulation efficiency of 76.54% and stability up to 60 days at 4 °C were prepared. The results of the biological study showed strong antibacterial properties of Thymol-based chitosan nanoparticles by reducing the expression of OmpA and PgaB biofilm genes at a significant level of P ≤ 0.05 and reducing antibiotic resistance compared to the free drug thymol and chitosan nanogels. Thymol-based chitosan nanogels at concentrations of 0.125 to 256μg/mL showed the lowest cytotoxicity against HEK-293 compared to chitosan and free Thymol nanogels. The results showed very strong antibacterial properties of Thymol-based chitosan nanogels against MDR strains such as Staphylococcus, Acinetobacter and Pseudomonas as the challenging bacteria of the century.


2021 ◽  
Author(s):  
Tohid Piri Gharaghie ◽  
Sheida Beiranvand ◽  
Neda Jegargoshe Shirin ◽  
Yalda Elahianfar ◽  
Somayeh Ghahari ◽  
...  

Abstract In the present study, the antibacterial and antibiofilm effects of Thymol-based chitosan nanogels were investigated. After clinical screening of MDR strains from the hospital environment, the morphological characteristics of the synthesized nanoparticles were identified using SEM, DLS, XRD and FTIR and the efficiency of encapsulation, stability and drug release were evaluated. The expression of OmpA and PgaB biofilm genes were determined by q-Real-Time PCR and the antibacterial and cytotoxic properties of the nanoparticles were determined by well diffusion and MTT methods, respectively. Nanoparticles with a size of 82.71 nm, encapsulation efficiency of 76.54% and stability up to 60 days at 4 °C were prepared. The results of the biological study showed strong antibacterial properties of Thymol-based chitosan nanoparticles by reducing the expression of OmpA and PgaB biofilm genes at a significant level of P ≤ 0.05 and reducing antibiotic resistance compared to the free drug thymol and chitosan nanogels. Thymol-based chitosan nanogels at concentrations of 0.125 to 256μg/mL showed the lowest cytotoxicity against HEK-293 compared to chitosan and free Thymol nanogels. The results showed very strong antibacterial properties of Thymol-based chitosan nanogels against MDR strains such as Staphylococcus, Acinetobacter and Pseudomonas as the challenging bacteria of the century.


2021 ◽  
Author(s):  
Tohid Piri Gharaghie ◽  
Sheida Beiranvand ◽  
Neda Jegargoshe Shirin ◽  
Yalda Elahianfar ◽  
Somayeh Ghahari ◽  
...  

Abstract In the present study, the antibacterial and antibiofilm effects of Thymol-based chitosan nanogels were investigated. After clinical screening of MDR strains from the hospital environment, the morphological characteristics of the synthesized nanoparticles were identified using SEM, DLS, XRD and FTIR and the efficiency of encapsulation, stability and drug release were evaluated. The expression of OmpA and PgaB biofilm genes were determined by q-Real-Time PCR and the antibacterial and cytotoxic properties of the nanoparticles were determined by well diffusion and MTT methods, respectively. Nanoparticles with a size of 82.71 nm, encapsulation efficiency of 76.54% and stability up to 60 days at 4 °C were prepared. The results of the biological study showed strong antibacterial properties of Thymol-based chitosan nanoparticles by reducing the expression of OmpA and PgaB biofilm genes at a significant level of P ≤ 0.05 and reducing antibiotic resistance compared to the free drug thymol and chitosan nanogels. Thymol-based chitosan nanogels at concentrations of 0.125 to 256μg/mL showed the lowest cytotoxicity against HEK-293 compared to chitosan and free Thymol nanogels. The results showed very strong antibacterial properties of Thymol-based chitosan nanogels against MDR strains such as Staphylococcus, Acinetobacter and Pseudomonas as the challenging bacteria of the century.


2020 ◽  
Vol 25 (44) ◽  
pp. 4717-4724
Author(s):  
Xiao-Ling Xu ◽  
Xu-Qi Kang ◽  
Jing Qi ◽  
Fei-Yang Jin ◽  
Di Liu ◽  
...  

Background: Antibacterial multidrug resistance has emerged as one of the foremost global problems affecting human health. The emergence of resistant infections with the increasing number of multidrug-resistant pathogens has posed a serious problem, which required innovative collaborations across multiple disciplines to address this issue. Methods: In this review, we will explain the mechanisms of bacterial multidrug resistance and discuss different strategies for combating it, including combination therapy, the use of novel natural antibiotics, and the use of nanotechnology in the development of efflux pump inhibitors. Results: While combination therapy will remain the mainstay of bacterial multi-drug resistance treatment, nanotechnology will play critical roles in the development of novel treatments in the coming years. Conclusion: Nanotechnology provides an encouraging platform for the development of clinically relevant and practical strategies to overcome drug resistance in the future.


2020 ◽  
Author(s):  
Tohid Piri Gharaghie ◽  
Sheida Biranvand ◽  
Neda Jegargoshe Shirin ◽  
Yalda Elahianfar ◽  
Somayeh Ghahari ◽  
...  

Abstract Introduction: The discovery of antibiotics for the treatment of bacterial infections was one of the most important advances in medical history, but unfortunately bacteria are highly adaptable, and overuse of antibiotics has made many bacteria resistant to antibiotics. In the present study, the antibacterial and antibiofilm effects of Thymol-based chitosan nanogels were investigated.Materials & Methods:After clinical screening of MDR strains from the hospital environment, the morphological characteristics of the synthesized nanoparticles were identified using SEM, DLS, XRD and FTIR and the efficiency of encapsulation, stability and drug release were evaluated. After determining the MIC concentration of nanoparticles, the expression of OmpA and PgaB biofilm genes were determined by q-Real-Time PCR and the antibacterial and cytotoxic properties of the nanoparticles were determined by well diffusion and MTT methods, respectively.Results:Three bacteria Pseudomonas, Acinetobacter and Staphylococcus were identified as MDR strains and the antibacterial and antibiofilm properties of nanoparticles with a size of 82.71 nm, encapsulation efficiency of 76.54% and stability up to 60 days at 4 °C were evaluated. The results of the biological study showed strong antibacterial properties of Thymol-based chitosan nanoparticles by reducing the expression of OmpA and PgaB biofilm genes at a significant level of P ≤ 0.05 and reducing antibiotic resistance compared to the free drug thymol and chitosan nanogels. Thymol-based chitosan nanogels at concentrations of 0.125 to 256μg/mL showed the lowest cytotoxicity against HEK-293 compared to chitosan and free Thymol nanogels.Discussion and Conclusion: The results of the study showed the very strong antibacterial properties of Thymol-based chitosan nanogels against MDR strains such as Staphylococcus, Acinetobacter and Pseudomonas as the challenging bacteria of the century. Therefore, the use of Thymol-based chitosan nanogels can be reported as a new application strategy with high potential in the pharmaceutical industry.


Author(s):  
Md. Abdullah Al Masud ◽  
Hamid Shaikh ◽  
Md. Shamsul Alam ◽  
M. Minnatul Karim ◽  
M. Abdul Momin ◽  
...  

Abstract Background The green synthesis strategy of metallic nanoparticles (NPs) has become popular due to being environmentally friendly. Stable silver nanoparticles (AgNPs) have been synthesized by natural products such as starch, soy protein, various extract of leaves, barks, and roots functioning both as reducing and stabilizing agents. Likewise, silk sericin (SS) is a globular protein discarded in the silk factory might be used for NP synthesis. In this research, we focus on the green synthesis and stabilization of AgNPs by SS as well as assessment of their antibacterial activities against some drug-resistant pathogen. Results SS was extracted from Bombyx mori silkworm cocoons in an aqueous medium. 17 w/w% of dry sericin powder with respect to the cocoon’s weight was obtained by freeze-drying. Furthermore, AgNPs conjugated to sericin, i.e., SS-capped silver nanoparticles (SS-AgNPs) were synthesized by easy, cost-effective, and environment-friendly methods. The synthesized SS-AgNPs were characterized by UV-visible spectroscopy, Fourier-transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, transmission electron microscopy (TEM), and X-ray diffraction measurement. It has been found from the absorbance of UV-visible spectroscopy that a higher percent of SS-AgNPs was obtained at a higher concentration of silver nitrate solution. FTIR-ATR spectra showed that the carboxylate groups obtained from silk sericin act as a reducing agent for the synthesis of silver nanoparticles, while NH2+ and COO− act as a stabilizer of AgNPs. The X-ray diffractogram of SS-AgNPs was quite different from AgNO3 and sericin due to a change in the crystal structure. The diameter of AgNPs was around 20–70 nm observed using TEM. The synthesized SS-AgNPs exhibited strong antibacterial activity against multidrug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 20μg/mL. Conclusions This study encourages the use of Bombyx mori for the ecofriendly synthesis of SS-AgNPs to control multidrug-resistant microorganisms.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bing Yuan ◽  
Jiaojiao Liu ◽  
Zhixiong Deng ◽  
Lin Wei ◽  
Wenwen Li ◽  
...  

AbstractAddressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG12k–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL−1), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.


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