Nano-ciprofloxacin/meropenem exhibit bactericidal activity against Gram-negative bacteria and rescue septic rat model

被引:1
作者
Hadiya, Safy [1 ]
Ibrahem, Reham A. [2 ]
Abd El-Baky, Rehab M. [2 ,3 ]
Elsabahy, Mahmoud [4 ,5 ]
Hussein, Abeer M. R. [6 ]
Tolba, Mohammed E. M. [7 ]
Aly, Sherine A. [8 ]
机构
[1] Assiut Univ, Al Rajhy Liver Hosp, Assiut Int Ctr Nanomed, Assiut 71515, Egypt
[2] Minia Univ, Fac Pharm, Dept Microbiol & Immunol, Al Minya 61511, Egypt
[3] Deraya Univ, Fac Pharm, Dept Microbiol & Immunol, Al Minya 61511, Egypt
[4] Badr Univ Cairo, Sch Biotechnol, Badr City 11829, Egypt
[5] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA
[6] Assiut Univ, Fac Med, Pharmacol Dept, Assiut 71515, Egypt
[7] Assiut Univ, Fac Med, Med Parasitol Dept, Assiut 71515, Egypt
[8] Assiut Univ, Fac Med, Dept Microbiol & Immunol, Assiut 71515, Egypt
关键词
bactericidal; ciprofloxacin; meropenem; nanoparticle; septic infections; synergy; LOADED CHITOSAN NANOPARTICLES; IN-VITRO; ACINETOBACTER-BAUMANNII; ANTIMICROBIAL AGENTS; COMBINATION; LEVOFLOXACIN; ANTIBACTERIAL; DELIVERY; SYNERGY; FLUOROQUINOLONE;
D O I
10.2217/nnm-2022-0314
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: We hypothesized that simultaneous administration of two antibiotics loaded into a nanopolymer matrix would augment their synergistic bactericidal interaction. Methods: Nanoplatforms of chitosan/Pluronic (R) loaded with ciprofloxacin/meropenem (CS/Plu-Cip/Mer) were prepared by the ionic gelation method, using Plu at concentrations in the range 0.5-4% w/v. CS/Plu-Cip/Mer was evaluated for antibacterial synergistic activity in vitro and in vivo. Results: CS/Plu-Cip and CS/Plu-Mer with Plu concentrations of 3% w/v and 2% w/v, respectively, exhibited similar to 80% encapsulation efficiency. The MICs of pathogens were fourfold to 16-fold lower for CS/Plu-Cip/Mer than for Cip/Mer. Synergy was evidenced for CS/Plu-Cip/Mer with a bactericidal effect (at 1x MIC and sub-MICs), and it significantly decreased bacterial load and rescued infected rats. Conclusion: This study illustrates the ability of CS/Plu nanopolymer to intensify synergy between antibiotics, thereby providing a promising potential to rejuvenate antibiotics considered ineffective against resistant pathogens. Antibiotics are used to treat bacterial infections. However, the more they are used, the less effective they become, because bacteria develop resistance to them. One strategy to overcome this is to treat bacterial infection with a combination of antibiotics that work well together. The antibiotics ciprofloxacin and meropenem are often given together to treat Pseudomonas aeruginosa, a bacterium which can cause sepsis, a type of blood poisoning. Another strategy to overcome antibiotic resistance is to load them into nanocarriers, which can change their properties. Nanocarrier-loaded antibiotics can reduce toxicity and increase effectiveness. This study investigated whether the effectiveness of this pair could be improved by loading them into nanoparticles. When these nanoparticles were given to rats with sepsis, they were significantly more effective than unloaded ciprofloxacin and meropenem combinations. These nanoparticles were also able to directly kill bacteria, rather than just prevent bacterial reproduction, as with the unloaded combination. This study demonstrates that nanocarrier loading can intensify the enhanced benefit of combined antibiotic treatments. This is a promising strategy to reuse antibiotics that have become ineffective at treating bacteria which have developed resistance. CS/Plu-Cip/Mer resulting in a bactericidal effect versus the Cip/Mer bacteriostatic effect. The CS/Plu-Cip/Mer resulted in statistically significant reductions in all measures tested in the septic rat model. Nano-Cip/Mer enhanced the survival rate and decreased the bacterial load in a septic rat model.
引用
收藏
页码:1553 / 1566
页数:14
相关论文
共 52 条
[1]   Ultrahigh antibacterial efficacy of meropenem-loaded chitosan nanoparticles in a septic animal model [J].
Abdelkader, Ayat ;
El-Mokhtar, Mohamed A. ;
Abdelkader, Ola ;
Hamad, Mostafa A. ;
Elsabahy, Mahmoud ;
El-Gazayerly, Omaima N. .
CARBOHYDRATE POLYMERS, 2017, 174 :1041-1050
[2]   Arabic gum plus colistin coated moxifloxacin-loaded nanoparticles for the treatment of bone infection caused by Escherichia coli [J].
Aguilera-Correa, J. J. ;
Gisbert-Garzaran, M. ;
Mediero, A. ;
Carias-Calix, R. A. ;
Jimenez-Jimenez, C. ;
Esteban, J. ;
Vallet-Regi, M. .
ACTA BIOMATERIALIA, 2022, 137 :218-237
[3]   Ag doped Sn3O4 nanostructure and immobilized on hyperbranched polypyrrole for visible light sensitized photocatalytic, antibacterial agent and microbial detection process [J].
Bahadoran, Ashkan ;
Baghbadorani, Nooshin Bahadoran ;
De Lile, Jeffrey Roshan ;
Masudy-Panah, Saeid ;
Sadeghi, Behzad ;
Li, Jinghan ;
Ramakrishna, Seeram ;
Liu, Qinglei ;
Janani, Baadal Jushi ;
Fakhri, Ali .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2022, 228
[4]   Activities of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with amikacin, against acinetobacters as determined by checkerboard and time-kill studies [J].
Bajaksouzian, S ;
Visalli, MA ;
Jacobs, MR ;
Appelbaum, PC .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (05) :1073-1076
[5]  
Brennan-Krohn T, 2018, ANTIMICROB AGENTS CH, V62, DOI [10.1128/AAC.00873-18, 10.1128/aac.00873-18]
[6]   Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void? [J].
Brown, David .
NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (12) :821-832
[7]  
Centers for Disease Control and Prevention, 2019, ANTIBIOTIC RESISTANC
[8]   A facile preparation method for efficiency a novel LaNiO3/SrCeO3 (p-n type) heterojunction catalyst in photocatalytic activities, bactericidal assessment and dopamine detection [J].
Chen, Ying ;
Jihad, Ali ;
Hussam, Fadhil ;
Al-Abdeen, Salah Hassan Zain ;
Hussein, Jamal Mohammad ;
Adhab, Zainab Hussein ;
Alzahraa, Zahraa Hamzaa Abd ;
Ahmad, Irfan ;
Fatolahi, Leila ;
Janani, Baadal Jushi .
SURFACES AND INTERFACES, 2023, 38
[9]   Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications [J].
Cheung, Randy Chi Fai ;
Ng, Tzi Bun ;
Wong, Jack Ho ;
Chan, Wai Yee .
MARINE DRUGS, 2015, 13 (08) :5156-5186
[10]   LL-37 protects rats against lethal sepsis caused by gram-negative bacteria [J].
Cirioni, O ;
Giacometti, A ;
Ghiselli, R ;
Bergnach, C ;
Orlando, F ;
Silvestri, C ;
Mocchegiani, F ;
Licci, A ;
Skerlavaj, B ;
Rocchi, M ;
Saba, V ;
Zanetti, M ;
Scalise, G .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2006, 50 (05) :1672-1679