Abstract
BackgroundCarbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates.ResultsThe obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2–3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively.ConclusionsThese promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.
Highlights
Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains develop a multi-resistance action to other potent antimicrobial agents
Shaaban et al J Nanobiotechnol (2017) 15:29 production pipelines, protection through a smart delivery system can potentiate the bactericidal efficacy of existing antibiotics and adequately address a solution to cease the current progression of resistant bacteria [5]
Mutation prevention concentration (MPC) The MPC was determined for IMP, IMP/poly Ɛ-caprolactone (PCL) and IMP/ PLGA according to the agar plate dilution procedures as reported previously by Credito et al [24]
Summary
The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2–3 h compared to the imipenem loaded PLGA and free drug. PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. The imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively
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