Thymol-based Chitosan Nanogels Have Strong Antibacterial and Anti-biofilm Effects on Multidrug-resistant Pathogens

Abstract

In the present study, the antibacterial and antibiofilm effects of Thymol-based chitosan nanogels were investigated. After clinical screening of MDR strains from the hospital environment, the morphological characteristics of the synthesized nanoparticles were identified using SEM, DLS, XRD and FTIR and the efficiency of encapsulation, stability and drug release were evaluated. The expression of OmpA and PgaB biofilm genes were determined by q-Real-Time PCR and the antibacterial and cytotoxic properties of the nanoparticles were determined by well diffusion and MTT methods, respectively. Nanoparticles with a size of 82.71 nm, encapsulation efficiency of 76.54% and stability up to 60 days at 4 °C were prepared. The results of the biological study showed strong antibacterial properties of Thymol-based chitosan nanoparticles by reducing the expression of OmpA and PgaB biofilm genes at a significant level of P ≤ 0.05 and reducing antibiotic resistance compared to the free drug thymol and chitosan nanogels. Thymol-based chitosan nanogels at concentrations of 0.125 to 256μg/mL showed the lowest cytotoxicity against HEK-293 compared to chitosan and free Thymol nanogels. The results showed very strong antibacterial properties of Thymol-based chitosan nanogels against MDR strains such as Staphylococcus, Acinetobacter and Pseudomonas as the challenging bacteria of the century.

Nanogel-based composites for bacterial antibiofilm activity: advances, challenges, and prospects

“…Hence, it can be inferred that encapsulating thymol in CS nanogels enhances its antibacterial properties, along with providing targeted drug delivery and controlled drug release. 44 2.1.3 Chitosan-based nanogels encapsulating essential oils. Several investigations have highlighted the versatile nature of CS-based nanogels, showcasing their capability to address multifaceted microbial challenges by encapsulating essential oils within the nanogel.…”

“…Thus, selecting a suitable vehicle carrying an appropriate natural compound with antibiofilm and antibacterial activities could be used to mitigate risks associated with multi-drug resistant strains. For instance, Gharaghie et al 44 explored the antibacterial and antibiofilm impacts of thymol-encapsulating CS nanogels. Thymol, a beneficial compound from the Thyme ( Thymus vulgaris L., Lamiaceae) plant, has well-established antimicrobial properties throughout its growth cycle.…”

“…Hence, it can be inferred that encapsulating thymol in CS nanogels enhances its antibacterial properties, along with providing targeted drug delivery and controlled drug release. 44 …”

“…18,43 Therefore, CS nanogels have been recently studied for the treatment of bacterial biolms. 11,17,44 2.1.1 Chitosan-based nanogels encapsulating synthetic antibiotics. Bacteria commonly possess negatively charged cell membranes, which are typically comprised of lipid layers and peptidoglycan.…”

“…52,53 Despite its effective antimicrobial properties, thymol faces limitations such as low water solubility, susceptibility to degradation, chemical reactivity, and volatilityinduced chemical and biological instability, restraining its effectiveness as an antimicrobial and preservative agent. 54 Consequently, Gharaghie et al 44 encapsulated thymol within CS nanogels with this encapsulation not only enhancing thymol's antibacterial and antibiolm qualities but also mitigating its cytotoxic attributes. Moreover, this encapsulation enhanced thymol's efficacy by enabling the thymol-loaded CS nanogels to adhere to the surface of bacterial biolms and employ controlled drug release mechanisms.…”