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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Ultrahigh antibacterial efficacy of meropenem-loaded chitosan nanoparticles in a septic animal model
Ayat Abdelkader1, Mohamed A El-Mokhtar2, Ola Abdelkader1
1Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut 71515, Egypt.
Abstract:
Antimicrobial resistance is one of the most significant health challenges worldwide. Meropenem is a broad spectrum beta-lactam antibiotic that possesses high activity against Gram-positive and Gram-negative bacteria. However, it has a short plasma half-life, and thus requiring frequent administration of high doses. For the first time, meropenem-loaded chitosan nanoparticles were prepared and evaluated as a potential tool to overcome antimicrobial resistance and to improve pharmacokinetics of the drug. Spherical nanosized particles were prepared and demonstrated ultrahigh encapsulation efficiency of meropenem (i.e. 76.3%). The nanoparticles could be stored in a freeze-dried powdered form while maintaining their physicochemical characteristics. In vitro, higher antibacterial activities of the drug-loaded nanoparticles were observed against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, as compared to the free drug. The nanoparticles were then tested in a septic rat model of Klebsiella pneumoniae and showed exceptional improvement of survival and bacterial clearance, as compared to the animals treated with the free drug. Hence, meropenem-loaded chitosan nanoparticles might have great potential for overcoming antimicrobial resistance.
Insights
Meropenem-loaded chitosan nanoparticles show enhanced antibacterial activity against resistant bacteria. This novel formulation improves drug delivery and survival rates in preclinical models, offering a promising strategy against antimicrobial resistance.
Area of Science:
- Nanotechnology
- Pharmacology
- Microbiology
Background:
- Antimicrobial resistance (AMR) is a major global health threat.
- Meropenem, a broad-spectrum antibiotic, has limitations due to its short plasma half-life, necessitating frequent high doses.
- Chitosan nanoparticles offer a potential platform for improved drug delivery and overcoming AMR.
Purpose of the Study:
- To develop and characterize meropenem-loaded chitosan nanoparticles (MCNs) for enhanced antimicrobial efficacy.
- To evaluate the pharmacokinetic and antibacterial properties of MCNs.
- To assess the therapeutic potential of MCNs in a preclinical model of bacterial sepsis.
Main Methods:
- Preparation and characterization of spherical meropenem-loaded chitosan nanoparticles.
- Determination of encapsulation efficiency and stability of MCNs.
- In vitro assessment of antibacterial activity against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.
- In vivo evaluation of MCNs in a Klebsiella pneumoniae septic rat model.
Main Results:
- Ultrahigh encapsulation efficiency (76.3%) of meropenem achieved in chitosan nanoparticles.
- MCNs demonstrated superior in vitro antibacterial activity compared to free meropenem.
- Freeze-dried MCNs maintained physicochemical stability.
- Significant improvement in survival rates and bacterial clearance in septic rats treated with MCNs.
Conclusions:
- Meropenem-loaded chitosan nanoparticles represent a promising approach to combat antimicrobial resistance.
- The nanoparticle formulation enhances meropenem's pharmacokinetic profile and therapeutic efficacy.
- MCNs offer a potential strategy to overcome existing challenges in antibiotic treatment.

