Antibiotic is the greatest invention at last century used to eradicate pathogens by reducing pathogen growth and destroying them [1–2]. Conventional antibiotics have drawbacks, such as multidrug-resistance (MDR) bacteria, minimum bioavailability, less diffusion capacity to the outer membrane, etc. . World health organization (WHO) defines these MDR bacteria as microorganisms that can grow in the presence of one or more antibiotics . The recovery from these MDR strains caused the healthcare-associated infection to become a more significant challenge day by day. High doses of antibiotics are administrated to overcome this challenge, which may generate toxic and adverse effects. A promising strategy to manage MDR bacteria-caused infections is applying nanoparticles (NPs) to restrain the MDR microorganism [5–7]. NPs can be the carrier of antibiotics and enhance the antibacterial activity of the antibiotics . This nanocarrier can enter cell's intracellular endocytic pathways and deliver the drug at a targeted position . The NP-based carrier for antibiotics significantly reduces the antibiotic doses required to eradicate pathogen several times than the dose of the free antibiotics.
S. typhimurium is a highly gram-negative pathogenic bacteria which causes salmonellosis for human and animals . The global concern about the treatment of S. typhimurium poses infection is day by day increasing due to its antibiotic resistance behavior. The antibiotic susceptibility properties of S. typhimurium were decreased, and this pathogen is resistant to chloramphenicol, tetracycline, streptomycin, ampicillin, etc. . For this reason, we choose ceftizoxime (CFX) (member of cephalosporin antibiotic group) to treat S. typhimurium caused the infection. CFX is a third-generation antibiotic which is effective for both gram-positive and gram-negative bacteria. The minimum amount of CFX requires to inhibit pathogenic growth for human body tissue causes different adverse effects . It is crucial to improve the therapeutic efficiency of CFX, which can be achieved by developing CFX loaded nano-drug carrier (NDC) with the minimum side effect . This NDC increases the therapeutic efficiency and reduces the drug consumption rate by the sustainable release of antibiotics. Different inorganic nanoparticles are widely used as carriers for antibiotics such as gold nanoparticles, silver nanoparticles, iron oxide nanoparticles, silica nanoparticles, zinc oxide nanoparticles, etc. Different biocompatible polymers are generally used in NDC for coating with nanoparticles to achieve specific targeted and sustainable release . We choose a noble NDC based on L-Cysteine (L-Cys) coated hollow Zinc oxide nanosphere to reduce antibiotic consumption. ZnO is a safe metal oxide approved by the US food and drug administration (FDA), suggesting the micro to larger size ZnO are generally safe, but nano shape might be toxic. It is accepted that discrete polymer coating on the surface of ZnO reduces its toxicity and makes it more efficient for drug delivery . Nano-shaped ZnO exhibited antibacterial properties over different pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, etc. [16–22]. A variety of nanostructured ZnO is generally used in the drug delivery system, such as quantum dots, nanospheres, nanoshells, nanosheets, nanorods, nano hollow spheres, nanobelts, and nanobelts, etc. Among them, nano hollow spheres take greater attention due to substantial internal space in their core. This core helps in drug transport, specific targeted drug delivery to the particular regime, and maintains release profile [23–24].
L-Cysteine (L-Cys) is a member of amino acid groups that are widely used in targeted drug delivery because of its active groups (carboxylic –COOH, amines –NH2, and thiol -SH). The thiol group present in L-Cys gives some exciting properties such as metal conjugating, damage skin repairing, and cross-linking . The three functional groups of L-Cys may interact with the ZnO sphere surface where the thiol group of L-Cys reacts with Zn2+ of ZnO and form a complex . L-Cys works as a scavenger free radical that create oxidative stress to cause cellular damage .
In this work, we present CFX loaded NDC named ZnO/L-Cys@CFX for controlled drug delivery for the growth inhibition of S. typhimurium. Here, the carrier matrix is L-Cys coated ZnO nano hollow sphere synthesized in simple and environmentally-friendly trisodium citrate assisted method. Finally, the antimicrobial test, such as the zone inhibition analysis and minimum inhibitory concentration (MIC) analysis, is carried out over S. typhimurium to characterize the NDC.