Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates

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.

Anti-carbapenamase activity of Camellia japonica essential oil against isolated carbapenem resistant klebsiella pneumoniae (MN396685)

“…Phenoloin is a acid derivatives formed by penicillins, which is hydrolytic opening of the β-lactum ring ( Maruthupandy et al, 2019 ). However, free phenol was easily attached with enzyme molecules and stimulate the color variation, which indicates that the PFEO has anti-carbapenemase activity ( Shaaban et al, 2017 ). Further, these evidences were confirmed by measurement of the transferred molecules into the phenol red added by using colorimeter analysis ( Seifert et al, 2018 ).…”

Nanotechnology approaches for global infectious diseases

“…4d). Shaaban et al developed poly(caprolactone) nanoparticles loaded with imipenem 82 and found that drug-loaded nanoparticles conferred 250-and 62.5-fold decreases in minimal inhibitory concentrations compared with free imipenem in in vitro cultures of imipenem-resistant K. pneumoniae and P. aeruginosa, respectively. Furthermore, to verify the ability of the nanocarriers to protect the drug from carbapenem-degrading enzymes, the imipenem formulations were tested with and without the addition of exogenous carbapenemase in Escherischia coli.…”

Emerging therapies against infections with Pseudomonas aeruginosa

“…Anti-pseudomonal drugs such as ciprofloxacin 103– 105 , meropenem 106 , tobramycin 107, 108 , gentamicin 109 , or amikacin 110 were encapsulated into liposomes or loaded into nanoparticles. The drug delivery systems were diverse in chemical nature and include anionic liposomes 105, 106, 109 , poly(lactic-co-glycolic) acid nanoparticles 110, 111 , water-soluble chitosan oligosaccharide conjugates 112 , oil-in-water cross-linked polymeric nanocomposites 113 , graphen-oxide conjugates 107 , or solid lipid nanoparticles 114 , to name just a few. Alternatively, dry powders 103, 104, 108, 115 or hydrogels 116– 119 were formulated or wound dressings were coated with a topical antimicrobial such as silver oxynitrate 120 .…”