Study on the therapeutic index and synergistic effect of Chitosan-zinc oxide nanomicellar composites for drug-resistant bacterial biofilm inhibition

Mehta, Mausam; Allen‐Gipson, Diane; Mohapatra, Shyam S.; Kindy, Mark S.; Limayem, Alya

doi:10.1016/j.ijpharm.2019.05.003

Cited by 10 publications

(10 citation statements)

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“…and ZnO alone. The nanoformulations, including chitosan nanoparticles, ZnO nanoparticles, and nanomicellar CZNPs were all tested at a concentration of 200 µg/mL, based on the most effective CZNPs concentration for eradicating the MDR biofilms built from previous studies (Limayem et al, 2016;Mehta et al, 2019;Mohapatra and Limayem, 2019). The resulting fluorescence values from the Biotek Synergy Neo2 microplate reader for each treatment were compared with the positive and negative controls.…”

Section: Resultsmentioning

confidence: 99%

“…The preparation of CZNPs nanomicelles as built upon from our previous studies (Limayem et al, 2015b;Mehta et al, 2019;Mohapatra and Limayem, 2019) and streamlined is as follows: to synthesize an optimized chitosan and ZnO lipid nonmicellar nanoformulation (Figures 1, 2), ZnO powder (∼18, 50, or 100 nm; Sigma Aldrich, St. Louis, MO) was dissolved in nano-purified water to prepare a solution of 1.42 mg/ml concentration (40 mg ZnO into 28 mL of water). This solution was sonicated for a minimum of 2-3 min to obtain a unified mixture.…”

Section: Preparation Of a Lipid-nanomicellar Cznp Joint Formulationmentioning

confidence: 99%

“…This further confirms the effectiveness of CZNPs synergism as opposed to chitosan and ZnO alone. Moreover, based on the previous study (Mehta et al, 2019), CZNPs were determined to be more therapeutic [therapeutic index (TI) = 1.2062] than Chitosan (TI = 0.3352) or ZnO (TI = 0.0429) alone. Thus, CZNPs synergism is proved to be more effective with minimal safe threshold toxicity when compared to ZnO and chitosan alone at the same concentrations, and is a promising nanotherapeutic in vivo agent in suppressing MDR biofilms.…”

Section: Advanced Fluorescent Microscopic Biofilm Observationsmentioning

confidence: 99%

“…Among the most promising nanotherapeutics, the newly designed CZNPs have been proven to have an extraordinary inhibitive potential against a substantial number of pathogens and MDR strains primarily nosocomial multidrug resistant Enterococcus faecium, Esherchia coli, and Pseudomonas spp. (Limayem et al, 2015a,b;Mehta et al, 2019;Mohapatra and Limayem, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…The nanomicellar joint CZNPs' uniqueness arise from their synergistic effects against a broad spectrum of MDR pathogens and flexibility to cope with different host cells depending on their structure, concentration, molecular weight, and size (Mohapatra and Limayem, 2019). As far as CZNPs go for the treatment of the gastrointestinal tract (GIT)-located MRFs, a nanomicellar structure was evidenced to be effective in vitro against biofilms formed in a 3D scaffold, mimicking the in vivo structure of the collagen matrix found in the GIT (Mehta et al, 2019). Based on this previous study, the effective dose at which 50% of the population are treated (ED50) of CZNPs against some multidrug resistance E. faecium CC17 biofilms was estimated to be 199.13 ug/mL, associated with a therapeutic index of 1.2062.…”

Section: Introductionmentioning

confidence: 99%

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A Streamlined Study on Chitosan-Zinc Oxide Nanomicelle Properties to Mitigate a Drug-Resistant Biofilm Protection Mechanism

Limayem

Patil

Mehta

et al. 2020

Front. Nanotechnol.

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The nosocomial multidrug resistant bacteria (MDR), are rapidly circulating from water surfaces to humans away from the clinical setting, forming a cyclical breeding ground of resistance, causing worldwide infections, and thus requiring urgent responses. The combination of chitosan and zinc oxide (CZNPs), with proven bactericidal effects on some MDRs, was further studied to set the stage for a broad-spectrum in vivo utilization of CZNPs. Toward ensuring CZNPs' uniformity and potency, when it faces not only biofilms but also their extracellular polymeric substances (EPS) defense mechanism, the size, zeta potential, and polydispersity index (PDI) were determined through dynamic light scattering (DLS). Furthermore, the efficacy of CZNPs was tested on the inhibition of MDR Gram-negative Escherichia coli BAA-2471 and Gram-positive Enterococcus faecium 1449 models, co-cultured in an Alvatex 3D fiber platform as a biofilm-like structure. The Biotek Synergy Neo2 fluorescent microplate reader was used to detect biofilm shrinkage. The biofilm protection mechanism was elucidated through detection of EPS using 3D confocal and transmission electronic microscopy. Results indicated that 200 μl/mL of CZNPs, made with 50 nm ZnO and 10,000 Da chitosan (N = 369.1 nm; PDI = 0.371; zeta potential = 22.8 mV), was the most promising nanocomposite for MDR biofilm reduction, when compared to CZNPs enclosing ZnO, 18 or 100 nm. This study depicts that CZNPs possess enough potency and versatility to face biofilms' defense mechanism in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Of a Lipid-nanomicellar Cznp Joint Formulationmentioning

confidence: 99%

Section: Advanced Fluorescent Microscopic Biofilm Observationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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