research interests

Using chemistry and bioengineering to develop Biomaterials for treating Infections, modulating Immune response and controlling Inflammation

My research interests lie in using chemistry to design and engineer soft bio- and nanomaterials for bio-active therapeutics and delivery. My research focus is to develop biomaterial and bioengineering strategies for the prevention and treatment of infectious and inflammatory diseases. In this regard, thus far, I have worked on developing molecular strategies guided by chemistry-based design principles to treat bacterial infections, attenuate inflammation for managing sepsis and induce an immune response against viral infections for vaccines.

Extracellular vesicles as biomaterials

Bio-engineered extracellular vesicles or exosomes for functional applications

Extracellualr vesicles (EVs) are biological nanoparticles, a class of cell-derived lipid nanovesicles (size = 30-500 nm), released by almost all the cell types including mammalian cells and bacteria. These lipid nanovesicles contain nucleic acids, proteins (both membrane and luminal) and many other molecules. EVs are nature's drug delivery carriers that transport nucleic acids, proteins and other molecular entities for cell-to-cell communication and signaling. EVs have been known to play important role in host-pathogen interactions, cancer metastasis and neurodegenerative diseases. My focus is to understand the role of EVs in host-bacteria interactions and develop bioengineered EVs for surface display of functional proteins using genetic manipulation of the producer cells. One of my projects involves development of bio-engineered EVs containing a functional protein on their membrane from transfected mammalian cells. Another project includes bio-engineered EVs from genetically engineered bacteria to display protein antigens for vaccine applications.

Selected publications in this area: ACS Appl. Mater. Interfaces., 2021, doi.org/10.1021/acsami.1c05108.

  • Understand the role of EVs in host-bacteria interactions

  • Bioengineered mammalian EVs displaying an innate immune receptor protein bind bacterial toxins

  • Detoxified and bioengineered bacterial EVs displaying protein antigens for vaccine applications

Biomaterials for vaccine delivery

Polymers for delivery of antiviral vaccines using microneedle skin patches

Local delivery such as the skin delivery of vaccines is promising because the dermal layers contain a pool of resident immune cells. Using microneedle array patches, vaccines can be delivered to skin. It has been shown that microneedle-based skin delivery of vaccines improves the immune response compared to traditional intramuscular administration. Using microneedle skin delivery patches, I have developed biomaterials-based approaches for i) improving the ambient temperature stability of whole virus vaccine and ii) controlled release of a multi-component protein subunit vaccine using polymer multilayers.

Selected publications in this area: J. Control. Release., 2020, 317, 130 ; Bioeng. Transl. Med., 2019, 4, e10127; ACS Nano 2018, 12, 10272

  • Microneedle arrays for delivery of whole virus and subunit protein vaccines against viral infections

  • Saccharide formulations improve ambient temperature stability of whole virus vaccine up to 1 month on microneedle arrays

  • Co-delivery of three-component vaccine from polymer multilayers (layer-by-layer assembly)

  • Controlled release of protein subunit antigens and adjuvants for up to 2 weeks

Antibacterial biomaterials

Cationic polymers targeting bacterial lipid membranes

Bacterial resistance to antibiotics is a burgeoning global health problem. Conventional antibiotics have specific binding targets in bacteria and hence, bacteria easily develop resistance by genetic mutations. Antimicrobial peptides (AMPs) are cationic and amphiphilic peptides that target the bacterial lipid membranes for which bacteria find it difficult to develop resistance. Such cationic amphiphilic molecules, in general, are selective to bacterial lipid membranes over the human red blood cell membranes because the former contain a greater proportion of negative charge compared to the latter. Inspired by these natural peptides, I have developed cationic-amphiphilic polymers that selectively kill bacteria.

Selected publications in this area: Biomaterials 2016, 74, 131; Chem. Sci. 2016, 7, 4613; Biomacromolecules. 2016, 17, 3094

  • Cationic amphiphilic polymers kill drug-resistant bacteria by disrupting membranes

  • Bacteria do not develop resistance to these membrane-disrupting polymers

  • Cationic polymers interact with bacterial lipid membranes through electrostatic, hydrophobic & hydrogen bonding interactions

  • Cationic polymers kill bacterial biofilms in vitro and in vivo

  • Cationic polymers act as antibiotic adjuvants to re-purpose the antibiotics to drug-resistant bacteria

  • Cationic polymers clear bacterial skin infections in mice models

Biomaterials for sepsis management

Cationic polymers and protein receptor-containing EVs

Sepsis is a life-threatening health condition due to excessive and harmful inflammation caused by a bacterial infection. Currently, one in five deaths is caused by sepsis, and 11 million people are dying from sepsis every year. Lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, is predominantly responsible for causing sepsis. I have developed molecular strategies to directly bind and neutralize LPS such that LPS-induced effects can be managed towards potential sepsis treatment. Two of such strategies include cationic polymers and receptor protein-containing bioengineered EVs.

Selected publications in this area: Biomacromolecules 2016, 17, 862; ACS Appl. Mater. Interfaces., 2021, doi.org/10.1021/acsami.1c05108.

  • Cationic polymers bind and neutralize anionic LPS through psuedoaggregate formation

  • Reduction in LPS-induced pro-inflammatory cytokine levels

  • Bio-engineered EVs expressing receptor proteins bind LPS

  • Neutralization of LPS-induced cytokine levels in vitro, ex vivo & in vivo

  • Decreased cell surface binding of LPS in presence of EVs