Research Projects

Nanomaterial-based antibacterial agents emerge as an alternative promising solution to combat drug-resistant bacteria and inhibit their proliferation. In recent years, several nanomaterial-based antibacterial agents have been reported based on metallic, metal oxide/sulfide nanoparticles, antibacterial peptides, carbon-based materials, etc. But most of them exhibit broad-spectrum antibacterial activity. Even though these broad-spectrum antibiotics are remarkable in combating multi-bacterial infections, they are effective for a short time. Also, the prolonged exposure to broad-spectrum antibiotics would disturb the balance of microbial flora at the site of infection, which may result in the development of drug-resistant bacteria and other health issues. In comparison to broad-spectrum antibiotics, selective antibacterial agents protect the host microbiome from collateral damage and avoid cross-resistance to non-targeted pathogens. So, the development of nanomaterial-based antibacterial agents for selective elimination of pathogenic bacteria is the most important parameter that is rarely developed. So, in this proposal we want to develop a series of surface-functionalized nanomaterials for specific/gram-selective antibacterial agents. Recently we have demonstrated this possibility by developing some functionalized nanomaterials that exhibited gram selectivity even in vivo. But that was mostly limited to only one type of nanomaterial and did not explore to various strains of bacteria. So, we want to expand these possibilities towards various platforms, approaches and applications. In the first approach, we will functionalize the selective nanomaterials, such as metal, metal oxide, and metal chalcogenide nanomaterials, for antibacterial activity both in vitro and in vivo. A few of those approaches will be, but not limited to, synthesis and functionalization of various stimuli-responsive ligands, development of tunable charged surfaces either by using dendrimers or short peptides, small-molecule conjugation, etc. Apart from therapeutic applications, these can also be used for antibacterial surface coating. The major challenges for the development of nanomaterial-based antibiotics for their biocompatibility, biodistribution, biodegradability etc. In this scenario, lipid-based carriers are emerging as highly effective nanocarriers for antibiotic delivery for its unique structure and biocompatibility. These vesicular systems consist of concentric lipid bilayers which encapsulate various therapeutic agents ranging from traditional drugs as well as nontraditional nanomaterials. Due to this unique ability of encapsulating and added biocompatibility, biodegradability, low toxicity, and absence of immune system activation, these are beneficial over other available delivery systems. Like nanomaterial surface functionalization, they can be conjugated with small molecules, charged functionality, antibodies, proteins, or enzymes, which help to administer a particular substance for targeted delivery, making them a potential candidate for targeted antibiotic delivery. To explore that, this proposed work will be associated with a series of lipid syntheses by considering various headgroups, linkers, and hydrophobic tails. In this proposal we will synthesize the boronic acid derivatives, gluconamide, and small peptides such as IK1 and IK4 peptides. Followed by that we will prepare and functionalize several hybrid nanomaterials and assess their antibacterial activity against gram-negative and gram-positive bacteria. After archiving selectivity, we will explore the mechanism of antibacterial activity by considering genotypic and phenotypic changes. After the toxicity assessment, we will finally evaluate their in vivo applicability in wound healing applications. This overall finding not only allows us to explore the development of alternative antibiotics but also may solve the problems associated with antibacterial drug resistivity.