Browsing by Author "Prem Shankar Gupta"

Now showing 1 - 6 of 6

Mesoporous polymeric nanoparticles for effective treatment of inflammatory diseases: an in vivo study
(Royal Society of Chemistry, 2025) Divya Pareek; Md Zeyaullah; Sukanya Patra; Oviya Alagu; Gurmeet Singh; Kirti Wasnik; Prem Shankar Gupta; Pradip Paik
Acute inflammatory diseases require suitable medicine over the existing therapeutics. In this line, the present work is focused on developing polymeric nanomedicine for the treatment of inflammatory disorders. Herein, cell viable nanoparticles (GlyNPs) of size 180-250 nm in diameter and pore size of 4-5 nm in diameter, based on glycine and acryloyl chloride, have been developed and proved to be a potential anti-inflammatory agent without using any conventional drugs. These particles exhibit colloidal stability (with a zeta potential of −35.6 mV). A network pharmacology-based computational study has been executed on 9076 genes and proteins responsible for inflammatory diseases, out of which 10 are selected that have a major role in rheumatoid arthritis (RA). In silico docking study has been conducted to find out the targeted efficiency of the GlyNPs considering 10 inflammation-specific markers, namely IL-6, IL-1β, TNF-α, TLR-4, STAT-1, MAPK-8, MAPK-14, iNOS, NF-κβ and COX-2. The results revealed that the GlyNPs could be an excellent anti-inflammatory component similar to aspirin. The in vitro inflammation activity of these GlyNPs has also been checked on an inflammation model generated by LPS in RAW 264.7 macrophages. Then, the in vitro anti-inflammation efficiency has been checked with 10-150 μg mL−1 of GlyNP doses. The treatment efficiency has been checked on inflammation-responsible immune markers (NO level, NF-κβ, INF-γ, IL-6, IL-10, and TNF-α) and it was found that the GlyNPs are an excellent component in reducing inflammation. The in vivo therapeutic response of GlyNPs on the induced rheumatoid arthritis (RA) model has been evaluated by measuring the morphological, biochemical and immune-cytokine and interferon levels responsible for the inflammation, using a 2 g kg−1 dose (sample to weight of rat). The anti-inflammatory efficiency of GlyNPs without using additional drugs was found to be excellent. Thus, GlyNPs could be paramount for the potential treatment of various inflammatory diseases. © 2025 The Royal Society of Chemistry.
Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration
(Royal Society of Chemistry, 2024) Kirti Wasnik; Prem Shankar Gupta; Gurmeet Singh; Somedutta Maity; Sukanya Patra; Divya Pareek; Sandeep Kumar; Vipin Rai; Ravi Prakash; Arbind Acharya; Pralay Maiti; Sudip Mukherjee; Yitzhak Mastai; Pradip Paik
Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G′, 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases. © 2024 The Royal Society of Chemistry.
Organ-targeted drug delivery systems (OTDDS) of poly[(N-acryloylglycine)-co-(N-acryloyl-l-phenylalanine methyl ester)] copolymer library and effective treatment of triple-negative breast cancer
(Royal Society of Chemistry, 2025) Sukanya Patra; None Jyotirmayee; Krishan Kumar; Divya Pareek; Prem Shankar Gupta; Anjali Ramsabad Mourya; Taniya Das; Kirti Wasnik; Malkhey Verma; Ruchi Chawla; Tarun K. Batra; Pradip Paik
Organ-targeted drug delivery systems (OTDDS) are essential for the effective treatment of complicated diseases. Triple-negative breast cancer (TNBC) is an aggressive cancer with high mortality and requires targeted therapeutics. This work was aimed at designing a library of polymeric OTDDS with N-acryloyl-glycine (NAG) and N-acryloyl-l-phenylalanine methyl ester (NAPA) [p(NAG-co-NAPA)(x:y)] and screening its in vivo organ-targeting specificity. Among this library, the best p(NAG-co-NAPA)(x:y) NPs with an x : y ratio of 1 : 4 and size of 160-210 nm targeted breasts to a high extent compared to other organs and thus were optimized for TNBC treatment. A network pharmacology study was performed, which revealed that 14 genes were responsible for TNBC, and a combination of DHA (targets 6 genes) and piperine (targets 8 genes) drugs was used to optimize the formulation, achieving the maximum therapeutic efficiency against TNBC with an IC50 value of 350 μg mL−1. The designed organ-specific polymeric nanoparticle (NP) library, identification of target genes and proteins responsible for TNBC, and the optimized formulation for effective combination therapy established an effective therapeutic option for TNBC. The findings of this work further demonstrate that this polymeric library of NPs shows exciting therapeutic potential for treating TNBC and presents innovative treatment options for critical diseases of the liver, heart, lungs and kidney. © 2025 The Royal Society of Chemistry.
Poly(N-acryloylglycine-acrylamide) Hydrogel Mimics the Cellular Microenvironment and Promotes Neurite Growth with Protection from Oxidative Stress
(American Chemical Society, 2023) Kirti Wasnik; Prem Shankar Gupta; Sudip Mukherjee; Alagu Oviya; Ravi Prakash; Divya Pareek; Sukanya Patra; Somedutta Maity; Vipin Rai; Monika Singh; Gurmeet Singh; Desh Deepak Yadav; Santanu Das; Pralay Maiti; Pradip Paik
In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly(N-acryloylglycine-acrylamide) [poly(NAG-b-A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG-b-A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG-b-A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3β inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG-b-A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells. © 2023 American Chemical Society.
Poly[(N-acryloyl glycine)-co-(acrylamide)]-induced cell growth inhibition in heparanase-driven malignancies
(Royal Society of Chemistry, 2025) Kirti Wasnik; Gurmeet Singh; Desh Deepak Yadav; Sukanya Patra; Prem Shankar Gupta; Alagu Oviya; Sandeep Kumar; Divya Pareek; Pradip Paik
In the present work, glycine, the monomer N-acryloylglycine (NAG), and polymeric units of poly[(N-acryloylglycine)-co-(acrylamide)] p(NAG-co-Ac) are examined using density functional theory (DFT), and experimental evidence is provided for their use in the therapy of cancer with a poor prognosis. Glycine plays a pivotal role in cell survival, and most anti-cancer agents alter glycine metabolomics and suppress cancer cell proliferation. Herein, we have utilized Frontier Molecular Orbital theory (FMO), and the results revealed that the introduction of acrylamide/divinyl benzene into the glycine-based polymer increased its biological activity by lowering the energy band gap. Heparanase and proteases are important in invasive tumor progression and worsening of prognosis. In this context, we have synthesized co-polymeric p(NAG-co-Ac) and revealed its protease inhibitory activities. It is revealed that the cross-linked homo-polymeric and cross-linked hetero-polymeric tetrameric arrangements inhibit heparanase activity via interacting at heparanase binding domain II (HBDII) with a docking score of ∼−11.08 kcal mol−1 (Ki) and at heparanase binding domain III (HBD III). The bathochromically shifted CD spectrum shows that the hydrogel interacts with heparanase and disturbs the secondary protein structure of the synthesized p(NAG-co-Ac) polymer. It is found that the synthesized p(NAG-co-Ac) hydrogel has anti-proliferative activity, acts as a migratory inhibitor of cancer cells, and favors programmed cell death. Further, the p(NAG-co-Ac) hydrogel exhibited anti-angiogenic behavior. In conclusion, p(NAG-co-Ac), with its anti-angiogenic and anti-tumorigenic capabilities, has a future as a potential anticancer polymer for the treatment of heparanase-driven invasive malignancies without using any additional anticancer drugs, and is promising for cancer treatment. © 2025 The Royal Society of Chemistry.
Targeted and Enhanced Antimicrobial Inhibition of Mesoporous ZnO-Ag2O/Ag, ZnO-CuO, and ZnO-SnO2Composite Nanoparticles
(American Chemical Society, 2021) Monica Pandey; Monika Singh; Kirti Wasnik; Shubhra Gupta; Sukanya Patra; Prem Shankar Gupta; Divya Pareek; Nyshadham Sai Naga Chaitanya; Somedutta Maity; Aramati B. M. Reddy; Ragini Tilak; Pradip Paik
In this work, mesoporous (pore size below 4 nm) composite nanoparticles of ZnO-Ag2O/Ag, ZnO-CuO, and ZnO-SnO2 of size d ≤ 10 nm (dia.) have been synthesized through the in situ solvochemical reduction method using NaBH4. These composite nanoparticles exhibited excellent killing efficacy against Gram-positive/negative bacterial and fungal strains even at a very low dose of 0.010 μg/mL. Additionally, by applying the in silico docking approach, the nanoparticles and microorganism-specific targeted proteins and their interactions have been identified to explain the best anti-bacterial/anti-fungal activities of these composites. For this purpose, the virulence and resistance causing target proteins such as PqsR, RstA, FosA, and Hsp90 of Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Candida albicans have been identified to find out the best inhibitory action mechanisms involved. From the in vitro study, it is revealed that all the composite nanoparticle types used here can act as potent antimicrobial components. All the composite nanoparticles have exhibited excellent inhibition against the microorganisms compared to their constituent single metal or metal oxide nanoparticles. Among the nanoparticle types, the ZnO-Ag2O/Ag composite nanoparticles exhibited the best inhibition activity compared to the other reported nanoparticles. The microorganisms which are associated with severe infections lead to the multidrug resistance and have become a huge concern in the healthcare sector. Conventional organic antibiotics are less stable at a higher temperature. Therefore, based on the current demands, this work has been focused on designing inorganic antibiotics which possess stability even under harsh conditions. In this direction, our developed composite nanoparticles were explored for potential uses in the healthcare technology, and they may solve many problems in global emergency and epidemics caused by the microorganisms. © 2021 The Authors. Published by American Chemical Society.