Page 43 - Biennial Report 2018-20 Jun 2021

are required not only to minimize the degradation and non-specific distribution of the cargoes
but also to maximize the therapeutic efficacy i.e. the delivery of the cargo at a specific site of
action thereby minimizing side effects. In the last few years, tremendous growth has been
recorded in the development of biomaterials for the delivery of bioactive substances
(conventional drugs, proteins, nucleic acids, etc.). During this period, Dr. Pradeep Kumar’s group
was also engaged in research activities towards design, synthesis, modifications and
characterization of polymeric and metallic nanoparticles showing these materials as safe and
efficient carriers for bioactive molecules with special emphasis on delivery of nucleic acids/drug
molecules. Recently, his group has developed some linear and branched polyethylenimine-based
cationic vectors for efficient transportation of genetic material across mammalian cells. In one
of such studies, linear polyethylenimine, a poor transfection reagent bearing secondary amines,
was conjugated with a variable amount of a ligand with a terminal boronic acid residue. The
resulting conjugates were characterized spectroscopically and shown to carry plasmid DNA more
efficiently than the native one. Enhanced uptake and internalization of the complexes were
found to be due to improved interactions of the complexes with the sialic acid expressed on the
surface of the cells, which facilitated endocytosis and transfection efficiency.

In another study, his group has demonstrated the importance of design and development of a
multifunctional carrier. Here, they have conjugated variable amounts of streptomycin, a broad-
spectrum antibacterial and antimycobacterial aminoglycoside, to low molecular weight
branched polyethylenimine and degree of substitution determined. Transfection studies showed
that the series of conjugates transfected the mammalian cells efficiently (~9-fold enhancement
with respect to native bPEI) exhibiting high cell viability too. Besides, the series of conjugates
displayed excellent antibacterial activity on pathogenic bacteria, even better than native
streptomycin on resistant strains. These results ensure the promising potential of the projected
multifunctional conjugates as safe and efficient gene delivery vectors as well as antibacterials for
future biomedical applications.

His group has also been working on the design and development of biocompatible nanomaterials
for drug delivery using an approach of molecular self-assembly. Use of substituted
polysaccharides for such applications offers the ease of design and synthesis and provides higher
biofunctionality and biocompatibility to nanomaterials. In the present work, the group focuses
on the synthesis, characterization, and potential biomedical applications of self-assembled
polysaccharide-based materials. They have demonstrated that the amphiphilic inulin self-
assembles in aqueous medium into nanostructures and encapsulates hydrophobic therapeutic
molecules, ornidazole. Hydrophophic dehydropeptide conjugation via a biocompatible ester
linkage makes it stable at a broader range of pH as well as against proteases. The resulting core-
shell type of nanostructures have been shown to encapsulate ornidazole in the hydrophobic core
and release it in a controlled fashion.

By taking the advantage of inulin, which gets degraded in the colon by colonic bacteria, the effect
of enzyme, inulinase, present in the microflora of the large intestine, on inulin-peptide
degradation followed by drug release has also been studied. Altogether, the group claims that
the projected amphiphilic inulin offers novel scaffold for the future design of nanostructures
with potential applications in the field of targeted drug delivery.

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