Browsing by Author "Kirti Wasnik"

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Advances in the Development of Biodegradable Polymeric Materials for Biomedical Applications
(Elsevier, 2022) Sukanya Patra; Monika Singh; Divya Pareek; Kirti Wasnik; Prem S. Gupta; Pradip Paik
Biodegradable polymers have a fascinated attention as a nanocarrier, scaffold, fibers, lenses, antibacterial dressing materials, gums, etc. for different biomedical applications. More than 200 types of natural and synthetic biodegradable polymers are reported. Herein this article the common biodegradable polymers that used in different biomedical fields have been summarized. Further, this includes polymer matrix, hydrogel, composites, copolymers and many others. Stability, degradation, mechanical behavior, thermal properties etc. are the major parameters considered for the development of novel biomaterials. This article includes the information about the different biopolymers, their advantages, disadvantages and recent advancements in the biomedical technology. © 2022 Elsevier Inc. All rights reserved.
Hollow mesoporous SiO2–ZnO nanocapsules and effective in vitro delivery of anticancer drugs against different cancers with low doses of drugs
(Elsevier Ltd, 2022) Gopabandhu Panigrahi; Himadri Medhi; Kirti Wasnik; Sukanya Patra; Premshankar Gupta; Divya Pareek; Somedutta Maity; Monica Mandey; Pradip Paik
Spherical hollow and mesoporous SiO2–ZnO nanocapsules were synthesized through sol-gel synthesis approach. Metabolic activity and biocompatibility of these nanocapules were tested and confirmed that SiO2–ZnO nanocapsules are not toxic. Small biomolecules and drug can be loaded into the nanoparticles since they are mesoporous with hollow core. Further these nanocapsules are capable of loading a huge amount of anticancer drugs such as imatinib and paclitaxel. The sustained release of the drugs demonstrated that these functionalized nanocapsules are useful for various therapeutic applications with precise release of drugs such as for the cancer therapy with low doses. To check the therapeutic efficiency of these nanocapsules, HeLa cells (cervical cancer cell line), breast cancer cell lines such as MCF-7 (primary breast cancer) and MDA-MB-231 (triple negative breast cancer cell lines) were used for the study. For all cells the therapeutic efficiencies obtained are better than the treatment efficiencies obtained with the administration of the free drugs and it was found that the low doses are required for the treatment once the drug molecules are formulated with these nanocapsules. Results directed us that in future these nanocapsules may have a huge clinical potential to treat various diseases. © 2022
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-acryloyl-l-phenylalanine) nanoparticles for potential treatment of inflammation in selective organs
(Royal Society of Chemistry, 2025) Divya Pareek; Sukanya Patra; Md Zeyaullah; Gurmeet Singh; Taniya Das; Prakriti Sundar Samanta; Aman Srikant Kudada; Anjali Ramsabad Mourya; Kirti Wasnik; Rajalaxmi Pradhan; Yitzhak Mastai; Pradip Paik
Systemic inflammation can lead to multi-organ failure. The existing anti-inflammatory agents show adverse side effects, and the present situation demands new drugs with high therapeutic efficiency. Polymeric nanoparticles based on amino acids could be one of the best alternative solutions due to their cytocompatibility and immune responses. Herein, we synthesized polymeric nanoparticles (Phe NPs) with a size of 20-30 nm using N-acryloyl-l-phenylalanine methyl ester as a precursor. The biological and immune responses of Phe NPs were found to be commanding, which was proven using immune cells (RAW 264.7 macrophages). In vitro study revealed an easy uptake of these NPs (∼98%) by the immune cells and that they can reduce inflammation by improving the immune response. In silico molecular docking results revealed that Phe NPs could potentially interact with immune cytokines such as IL-6, NF-κβ, TNF-α, COX2 and IL-1β. Phe NPs exhibit a similar type of binding and interaction as ibuprofen (IBF), which confirms its immune response to control inflammation. The anti-inflammatory response of Phe NPs was established through an in vitro inflammation model developed using LPS-stimulated RAW 264.7 macrophages. Furthermore, an LPS-induced in vivo rat model was developed, which revealed that Phe NPs are useful for the treatment of systemic inflammation. Blood-based biochemical parameters such as C-reactive protein, lactate and procalcitonin levels were determined, and the anti-inflammatory responses of Phe NPs were confirmed through RT-PCR analysis by measuring the levels of inflammatory markers such as TNF-α, IL-6 and VEGF. Finally, an in vivo systemic inflammation rat model was used to examine the systemic organs (brain, liver, kidneys, spleen, lungs and heart) before and after treatment with Phe NPs to prove their anti-inflammatory responses. H&E histological analysis of different organs further revealed that even at a low dose of 100 μg kg−1, Phe NPs are immune-responsive/protective and anti-inflammatory in nature. © 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.
Synthesized Gold Nanoparticles with Moringa Oleifera leaf Extract Induce Mitotic Arrest (G2/M phase) and Apoptosis in Dalton’s Lymphoma Cells
(Springer, 2024) Sandeep Kumar; Alok Shukla; Surya Pratap Singh; Rishi Kant Singh; Anand Kumar Patel; Praveen Kumar Verma; Sanjay Kumar; Naveen Kumar; Varsha Singh; Kirti Wasnik; Arbind Acharya
The therapeutic potential of chemically synthesized AuNPs has been demonstrated in various types of cancer. However, gold nanoparticles (AuNPs) synthesized using typical chemical methods have concerns regarding their environmental safety and adverse impact on human well-being. To overcome this issue, we used an environmentally friendly approach in which gold nanoparticles were synthesized using Moringa oleifera leaf extract (MLE). The present research was mainly focused on the biosynthesis and characterization of gold nanoparticles (AuNPs) using Moringa oleifera leaf extract (MLE-AuNPs) and explore its anticancer potential against Dalton’s Lymphoma (DL) cells. Characterization of the MLE-AuNPs was conducted using UV-Vis Spectroscopy to confirm the reduction process, FTIR analysis to ascertain the presence of functional groups, and XRD analysis to confirm the crystallinity. SEM and TEM images were used to examine size and morphology. After characterization, MLE-AuNPs were evaluated for their cytotoxic effects on Dalton’s lymphoma cells, and the results showed an IC50 value of 75 ± 2.31 µg/mL; however, there was no discernible cytotoxicity towards normal murine thymocytes. Furthermore, flow cytometric analysis revealed G2/M phase cell cycle arrest mediated by the downregulation of cyclin B1 and Cdc2 and upregulation of p21. Additionally, apoptosis induction was evidenced by Annexin V Staining, accompanied by modulation of apoptosis-related genes including decreased Bcl-2 expression and increased expression of Bax, Cyt-c, and Caspase-3 at both the mRNA and protein levels. Collectively, our findings underscore the promising anti-cancer properties of MLE-AuNPs, advocating their potential as a novel therapeutic avenue for Dalton’s lymphoma. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
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.
Targeted specific inhibition of bacterial and: Candida species by mesoporous Ag/Sn-SnO2composite nanoparticles: In silico and in vitro investigation
(Royal Society of Chemistry, 2022) Monica Pandey; Kirti Wasnik; Shubhra Gupta; Monika Singh; Sukanya Patra; Premshankar Gupta; Divya Pareek; Somedutta Maity; Ragini Tilak; Pradip Paik
Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn-SnO2 composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn-SnO2 nanoparticles on adhesion and invasion responsible molecular targets such as LpfD (E. coli), Als3 (C. albicans) and on virulence/resistance causing PqsR (P. aeruginosa), RstA (Bmfr) (A. baumannii), FoxA (K. pneumonia), Hsp90 and Cyp51 (C. albicans). These Ag/Sn-SnO2 nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans, which are the highest ever reported results. Further, Ag/Sn-SnO2 NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn-SnO2 nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics. © The Royal Society of Chemistry.