ayushi priyam | Deakin University (original) (raw)

Papers by ayushi priyam

Research paper thumbnail of Hemocompatibility of biogenic phosphorus nano-agromaterials at environmentally relevant and supra-environmental concentrations for occupational exposure

Environmental Science: Advances

Physico-chemically different and agriculturally relevant phosphorus-based nanomaterials are hemoc... more Physico-chemically different and agriculturally relevant phosphorus-based nanomaterials are hemocompatible and acquire bio-corona on interaction with human blood.

Research paper thumbnail of Application of Metallic Nanoparticles as Agri Inputs: Modulation in Nanoparticle Design and Application Dosage Needed #

CRC Press eBooks, Sep 27, 2022

Research paper thumbnail of Multi-endpoint assessments for in vitro nano-bio interactions and uptake of biogenic phosphorus nanomaterials using HEK293 cells

Environmental Science: Advances

Phosphorus (P)-based nanomaterials (NMs) are now explored to be used as nanofertilisers due to hi... more Phosphorus (P)-based nanomaterials (NMs) are now explored to be used as nanofertilisers due to higher uptake in plants, enhanced nutrient use efficiency and minimal leaching. However, their colloidal behaviour in...

Research paper thumbnail of Uptake and Benefits of Biogenic Phosphorus Nanomaterials Applied via Fertigation to Japonica Rice (Taipei 309) in Low- and High-Calcareous Soil Conditions

ACS Agricultural Science & Technology

Research paper thumbnail of Fertilizing benefits of biogenic phosphorous nanonutrients on Solanum lycopersicum in soils with variable pH

Heliyon, 2022

Nanoformulations of Phosphorous (P) have recently been proposed as alternatives to P fertilizers.... more Nanoformulations of Phosphorous (P) have recently been proposed as alternatives to P fertilizers. In this study, the fertilizing efficacies of P-based nanomaterials (NMs), nanohydroxyapatite (nHAP) and nanophosphorus (nP), were examined on Solanum lycopersicum (Pusa Rohini, Indian tomato) in growth room pot experiments. These NMs differed in their mode of synthesis, chemical composition, size and shape. Rock-phosphate (RP), phosphoric acid (PA) and di-ammonium phosphate (DAP) were included as bulk materials for comparison. Three varieties of artificial soils were included in the study, neutral (pH 7.2), acidic (pH 4.3) and basic (pH 9.8). The effects of the NMs on germination, plant growth, and P content were assessed at the 15 th and 30 th days after treatment. The results showed that P-based NMs enhance the overall germination and plant growth by increasing P levels in all types of soils for the tomato plants in comparison to the bulk P sources. Analysis using X-ray fluorescence revealed enhanced P content in the plants indicating the uptake of P-based NMs. Evaluation of H 2 O 2 , total phenolics and total flavonoids contents after NM treatment suggest that there is no stress caused due to the application of NMs to the plant. The results of this study indicate the beneficial role of P-based NMs as fertilizers at the early stages of plant development, which opens a scope for further investigation of underlying metabolic and molecular pathways and field trials.

Research paper thumbnail of Exposure to biogenic phosphorus nano-agromaterials promotes early hatching and causes no acute toxicity in zebrafish embryos

Environmental Science: Nano, 2022

With a growing number of studies now exploring the development of novel phosphorous (P)-based nan... more With a growing number of studies now exploring the development of novel phosphorous (P)-based nanomaterials (NMs) for agriculture, there is an increasing concern that these NMs may enter aquatic environments after use and affect aquatic organisms.

Research paper thumbnail of Abiotic factors and aging alter the physicochemical characteristics and toxicity of Phosphorus nanomaterials to zebrafish embryos

Research paper thumbnail of Investigation into the trophic transfer and acute toxicity of phosphorus-based nano-agromaterials in Caenorhabditis elegans

NanoImpact, 2021

Abstract Biogenic phosphorus (P) based – nanomaterials (NMs) are currently being explored as nano... more Abstract Biogenic phosphorus (P) based – nanomaterials (NMs) are currently being explored as nanofertilizers. In this study, the acute toxic effects and trophic transfer of multiple types of P-based NMs were examined on soil-dwelling nematode, Caenorhabditis elegans. The study involved four variants of nanohydroxyapatites (nHAPs) synthesized either via a biogenic or a chemical route and another NM, nanophosphorus (nP), biosynthesized from bulk rock phosphate (RP). The pristine NMs differed in their physicochemical properties with each possessing different shapes (biogenic nHAP: platelet-shaped, ˜35 nm; biogenic nP, ˜5–10 nm: dots; chemically synthesized nHAPs: spherical, ˜33 nm, rod, ˜80 nm and needle-shaped, ˜64 nm). The toxic effects of NMs' in C. elegans were assessed using survival, hatching and reproductive cycle as the key endpoints in comparison to bulk controls, calcium phosphate and RP. The interactions and potential uptake of fluorescent-tagged nHAP to E. coli OP50 and C. elegans were investigated using confocal microscopy. The transformation of NMs within the nematode gut was also explored using dynamic light scattering and electron microscopy. C. elegans exposed to all of the variants of nHAP and the nP had 88–100% survival and 82–100% hatch rates and insignificant effects on brood size as observed at the tested environmentally relevant concentrations ranging from 5 to 100 μg.mL−1. Confocal microscopy confirmed the interaction and binding of fluorescent-tagged nHAP with the surface of E. coli OP50 and their trophic transfer and internalization into C. elegans. Interestingly, there was only a small reduction in the hydrodynamic diameter of the nHAP after their uptake into C. elegans and the transformed NMs did not induce any additional toxicity as evident by healthy brood sizes after 72 h. This study provides key information about the environmental safety of agriculturally relevant P-based NMs on non-target species.

Research paper thumbnail of In Vitro Assessment of Core-Shell Micellar Nanostructures of Amphiphilic Cationic Polymer-Peptide Conjugates as Efficient Gene and Drug Carriers

Journal of Pharmaceutical Sciences, 2020

Design and development of biocompatible, biodegradable and stable dual delivery systems for drug ... more Design and development of biocompatible, biodegradable and stable dual delivery systems for drug and gene is the need of the hour. Here, we have designed a strategy to develop carrier systems consisting of above mentioned properties by (a) incorporating an unnatural amino acid in the peptide backbone, and b) conjugating a low molecular weight cationic polymer (polyethylenimine, PEI) for incorporating cationic charge. Using this strategy, we have synthesized a small series of Boc-FΔF-AH-polyethylenimine conjugates by varying the concentration of Boc-FΔF-aminohexanoic acid, viz., PP-1, PP-2 and PP-3. These conjugates self-assembled in aqueous medium to form micelles in the size range of ∼144-205 nm with zeta potential ∼ +7.9-14.2 mV bearing core-shell type of conformation. Positive surface of the micelles facilitated the binding of plasmid DNA as well as transportation inside the cells. The hydrophobic core of the nanostructures helped in the encapsulation of the hydrophobic drug molecule, which was then got released in a controlled manner. DNA complexes of the conjugates were not only found non-toxic but also exhibited higher transfection efficacy than the native polymer and Lipofectamine. Altogether, these nanostructures are capable of delivering a drug and a gene simultaneously in vitro and could be used as next-generation delivery agents.

Research paper thumbnail of A new method for biological synthesis of agriculturally relevant nanohydroxyapatite with elucidated effects on soil bacteria

Scientific Reports, 2019

The study describes a novel and environment friendly route of biosynthesis of nanohydroxyapatite ... more The study describes a novel and environment friendly route of biosynthesis of nanohydroxyapatite (nHAP). Bacillus licheniformis mediated synthesis of nHAP has been carried out with different phosphate concentrations (2%, 5%, 10% and 20% w/v) of potassium dihydrogen orthophosphate monobasic (K2HPO4). The synthesis is supported by a two-step mechanism – (i) solubilization of P by organic acids extracellularly secreted by the bacterial strain and (ii) gelation of P and Ca. The nHAP particles were characterized using electron microscopy and XRD analysis. Powdered crystalline particles with a size range of 30 ± 5 nm were obtained with shape and size dependent on phosphate concentrations. The particles showed no adverse effect on plant growth-promoting bacteria. Evaluation of nHAP prepared by this route with 2% P source provides scope for a wide range of applications, especially as a nano-fertilizer.

Research paper thumbnail of Polydopamine –aminoglycoside nanoconjugates: Synthesis, characterization, antimicrobial evaluation and cytocompatibility

Materials Science and Engineering: C, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Iron chelator Deferoxamine protects human neuroblastoma cell line SH-SY5Y from 6-Hydroxydopamine-induced apoptosis and autophagy dysfunction

Journal of Trace Elements in Medicine and Biology, 2019

Background: Intracellular iron involves in Fenton's reaction-mediated Hydroxyl radical (OH•) gene... more Background: Intracellular iron involves in Fenton's reaction-mediated Hydroxyl radical (OH•) generation by reacting with the neurotoxic agent 6-Hydroxydopamine (6-OHDA) autoxidation derivative Hydrogen Peroxide (H 2 O 2). Several studies have been conducted so far on the neuroprotective activities of the iron chelator Deferoxamine (DFO) but little or no clear evidence about the underlying cellular mechanism is available. Methods: The present study was conducted on Human neuroblastoma cell line SH-SY5Y in the absence or presence of 6-OHDA or H 2 O 2 and / or DFO. Following incubation, cell viability assay, intracellular reactive oxygen species (ROS) determination, flow cytometric quantification of apoptotic cells followed by nuclear staining, intracellular tracking of transfected fusion construct of microtubule-associated protein 1B-light chain with Green fluorescent protein-Red fluorescent protein (LC3B-GFP-RFP reporters) and immunocytochemistry of intracellular Cathepsin protein by confocal microscopy, were conducted. In addition, western blotting was carried out to detect expressions of apoptotic and autophagy related proteins. Results: This study confirmed the neuroprotective potential of DFO by inhibiting 6-OHDA-mediated cell death and ROS generation. Reduced percentage of apoptotic cells and appearance of altered nuclei architecture followed by a reduced expression of cleaved PARP (Poly-ADP-ribose Polymerase) and cleaved Caspase-3 were observed upon DFO treatment against 6-OHDA, and as well as against H 2 O 2 in SH-SY5Y cell lines. Besides, DFO induced the intracellular autophagolysosome formation (red puncta) rather than autophagosome (yellow puncta) only. Thereafter it was observed that DFO restored the expression of intracellular lysosomal protease Cathepsin and reduced the expression of the LC3-II. Conclusion: Taken together, this study clearly demonstrated that the anti-Fenton activity of DFO inhibited apoptosis and caused blockade in ALP or autophagy dysfunction in SH-SY5Y cell lines. These outcomes further suggest that DFO provides neuroprotection by inhibiting apoptosis and inducing the progression of Autophagylysosomal pathway (ALP).

Research paper thumbnail of Enhanced solubility and self-assembly of amphiphilic sulfasalazine-PEG-OMe (S-PEG) conjugate into core-shell nanostructures useful for colonic drug delivery

Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2018

Recently, several studies have been undertaken to formulate drugs in soluble state leading to enh... more Recently, several studies have been undertaken to formulate drugs in soluble state leading to enhanced bioavailability as well as to provide controlled drug release. Because of their distinct advantages, such systems have attracted increasing attention of the researchers. Here, sulfasalazine, a drug used to treat inflammatory bowel disease, was conjugated with a low molecular weight polyethylene glycol monomethyl ether (750 Da) to obtain amphiphilic sulfasalazine-polyethylene glycol (S-PEG) conjugate, which not only showed enhanced solubility but also, on self-assembly, generated core-shell type micellar nanostructures with hydrophobic core and hydrophilic shell. Post-physicochemical characterization, these micellar nanostructures were used to entrap hydrophobic drug molecules, ornidazole and sulfasalazine. The drug-entrapped S-PEG nanoformulations showed controlled release of drugs at pH 7.2 making these nanoformulations ideal for colon-targeted drug delivery. Further, azo-moiety bearing sulfasalazine conjugate showed responsiveness to a chemical reductant, sodium dithionite, which mimics azoreductase enzymes present in the colonic microflora. Drug release in the presence of sodium dithionite increased significantly ensuring the potential of these formulations for colon-targeted drug delivery.

Research paper thumbnail of Understanding the safety aspect of biologically synthesized agriculturally useful nanomaterials for humans and environment

Frontiers in Nanoscience and Nanotechnology, 2018

Research paper thumbnail of Role of Endocrine-Disrupting Engineered Nanomaterials in the Pathogenesis of Type 2 Diabetes Mellitus

Frontiers in Endocrinology, 2018

Keywords: engineered nanomaterial (ENM), type 2 diabetes mellitus (T2DM), endocrine disruptor, in... more Keywords: engineered nanomaterial (ENM), type 2 diabetes mellitus (T2DM), endocrine disruptor, insulin resistance, reduced insulin sensitivity, oxidative stress, in vitro and in vivo studies, epidemiological evidences BACKGROUND Materials acquire unique characteristics when the size of the particle is reduced to nanoscale. Nanomaterials (NMs) are a universal set of nanoscale materials having at least one of the dimensions in the nano-range. With having at least one dimension in nanoscale as a common feature, nanoparticles, nanowires, nanosheets, nanotubes, and nanoplates can be stated as the key subsets of NMs (1). The various properties of a nanomaterial (NM), including its melting point, electrical conductivity, magnetic permeability, chemical reactivity and fluorescence, are determined by the particle size (2). Sizereduction of a material to nanoscale enhances its functional aspects and associated technological benefits. Therefore, the use of engineered nanomaterials (ENMs) in the development of advanced technologies for medicine, engineering and natural sciences has significantly increased since the start of the twentyfirst century (3). ENMs are being incorporated into our everyday routine as a part of clothing, food, cosmetics, medicines,

Research paper thumbnail of Mussel-inspired polydopamine-polyethylenimine conjugated nanoparticles as efficient gene delivery vectors for mammalian cells

Colloids and surfaces. B, Biointerfaces, Jan 26, 2017

Efficient delivery of DNA to cells is the primary concern to address the objective of gene therap... more Efficient delivery of DNA to cells is the primary concern to address the objective of gene therapy. Many attempts have been made to develop polymeric carriers for gene delivery. To have an efficient carrier, it is vital to understand the properties of the vector for better stability, transfection efficiency and minimal toxicity. Branched polyethylenimine (bPEI) has been considered as the 'gold standard' for gene delivery but suffers a major drawback of exhibiting high cytotoxicity. Here, we have attempted to develop a mussel-derived polymer, polydopamine (PDA), conjugated polyethylenimine nanoparticles in such a way that the toxic nature of bPEI is suppressed by the conversion of free primary amine groups to secondary and tertiary amines. Keeping the amount of PDA fixed, varying amounts of bPEIs of different molecular weights (25, 10 and 1.8kDa) were conjugated via Michael addition and/or Schiff base. A trend in hydrodynamic size of the conjugated nanoparticles was observed ...

Research paper thumbnail of Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole

International journal of biological macromolecules, Jan 14, 2017

Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompat... more Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, a unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the h...

Research paper thumbnail of Ligands with Delocalized Charge Density and Hydrophobicity Significantly Affect the Transfection Efficacy of the PAMAM Dendrimer

Pharmaceutical Nanotechnology, 2015

Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic aci... more Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic acids to the cells. However, these dendrimers cause a significant amount of cytotoxicity. In order to improve its transfection efficiency and cell viability, surface amine groups of PAMAM were converted into guanidinium (Gn) and tetramethylguanidi-nium (TMG) moieties. These modified PAMAM dendrimers interacted with negatively charged plasmid DNA efficiently and formed stable complexes as revealed by dynamic light scattering analysis. PAMAM/pDNA, PAMAM-TMG/pDNA and PAMAM-Gn/pDNA complexes were found to be in the range of 175-250 nm with zeta potential in the range of +21-37 mV. Further, these modified dendrimers did not display toxicity rather it decreased a bit when tested in HEK293, HeLa and MCF-7 cells. Among these modified dendrimers, PAMAM-Gn/pDNA complex displayed the highest transfection efficiency in both the cell lines HEK293 and MCF-7.

Research paper thumbnail of Ligands with Delocalized Charge Density and Hydrophobicity Significantly Affect the Transfection Efficacy of the PAMAM Dendrimer

Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic aci... more Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic acids to the cells. However, these dendrimers cause a significant amount of cytotoxicity. In order to improve its transfection efficiency and cell viability, surface amine groups of PAMAM were converted into guanidinium (Gn) and tetramethylguanidi-nium (TMG) moieties. These modified PAMAM dendrimers interacted with negatively charged plasmid DNA efficiently and formed stable complexes as revealed by dynamic light scattering analysis. PAMAM/pDNA, PAMAM-TMG/pDNA and PAMAM-Gn/pDNA complexes were found to be in the range of 175-250 nm with zeta potential in the range of +21-37 mV. Further, these modified dendrimers did not display toxicity rather it decreased a bit when tested in HEK293, HeLa and MCF-7 cells. Among these modified dendrimers, PAMAM-Gn/pDNA complex displayed the highest transfection efficiency in both the cell lines HEK293 and MCF-7.

Research paper thumbnail of Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole

Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompat... more Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486 nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, an unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the hydrophobic core and released 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 been studied. Altogether, small peptide conjugated to inulin offers novel scaffold for the future design of nanostructures with potential applications in the field of targeted drug delivery.

Research paper thumbnail of Hemocompatibility of biogenic phosphorus nano-agromaterials at environmentally relevant and supra-environmental concentrations for occupational exposure

Environmental Science: Advances

Physico-chemically different and agriculturally relevant phosphorus-based nanomaterials are hemoc... more Physico-chemically different and agriculturally relevant phosphorus-based nanomaterials are hemocompatible and acquire bio-corona on interaction with human blood.

Research paper thumbnail of Application of Metallic Nanoparticles as Agri Inputs: Modulation in Nanoparticle Design and Application Dosage Needed #

CRC Press eBooks, Sep 27, 2022

Research paper thumbnail of Multi-endpoint assessments for in vitro nano-bio interactions and uptake of biogenic phosphorus nanomaterials using HEK293 cells

Environmental Science: Advances

Phosphorus (P)-based nanomaterials (NMs) are now explored to be used as nanofertilisers due to hi... more Phosphorus (P)-based nanomaterials (NMs) are now explored to be used as nanofertilisers due to higher uptake in plants, enhanced nutrient use efficiency and minimal leaching. However, their colloidal behaviour in...

Research paper thumbnail of Uptake and Benefits of Biogenic Phosphorus Nanomaterials Applied via Fertigation to Japonica Rice (Taipei 309) in Low- and High-Calcareous Soil Conditions

ACS Agricultural Science & Technology

Research paper thumbnail of Fertilizing benefits of biogenic phosphorous nanonutrients on Solanum lycopersicum in soils with variable pH

Heliyon, 2022

Nanoformulations of Phosphorous (P) have recently been proposed as alternatives to P fertilizers.... more Nanoformulations of Phosphorous (P) have recently been proposed as alternatives to P fertilizers. In this study, the fertilizing efficacies of P-based nanomaterials (NMs), nanohydroxyapatite (nHAP) and nanophosphorus (nP), were examined on Solanum lycopersicum (Pusa Rohini, Indian tomato) in growth room pot experiments. These NMs differed in their mode of synthesis, chemical composition, size and shape. Rock-phosphate (RP), phosphoric acid (PA) and di-ammonium phosphate (DAP) were included as bulk materials for comparison. Three varieties of artificial soils were included in the study, neutral (pH 7.2), acidic (pH 4.3) and basic (pH 9.8). The effects of the NMs on germination, plant growth, and P content were assessed at the 15 th and 30 th days after treatment. The results showed that P-based NMs enhance the overall germination and plant growth by increasing P levels in all types of soils for the tomato plants in comparison to the bulk P sources. Analysis using X-ray fluorescence revealed enhanced P content in the plants indicating the uptake of P-based NMs. Evaluation of H 2 O 2 , total phenolics and total flavonoids contents after NM treatment suggest that there is no stress caused due to the application of NMs to the plant. The results of this study indicate the beneficial role of P-based NMs as fertilizers at the early stages of plant development, which opens a scope for further investigation of underlying metabolic and molecular pathways and field trials.

Research paper thumbnail of Exposure to biogenic phosphorus nano-agromaterials promotes early hatching and causes no acute toxicity in zebrafish embryos

Environmental Science: Nano, 2022

With a growing number of studies now exploring the development of novel phosphorous (P)-based nan... more With a growing number of studies now exploring the development of novel phosphorous (P)-based nanomaterials (NMs) for agriculture, there is an increasing concern that these NMs may enter aquatic environments after use and affect aquatic organisms.

Research paper thumbnail of Abiotic factors and aging alter the physicochemical characteristics and toxicity of Phosphorus nanomaterials to zebrafish embryos

Research paper thumbnail of Investigation into the trophic transfer and acute toxicity of phosphorus-based nano-agromaterials in Caenorhabditis elegans

NanoImpact, 2021

Abstract Biogenic phosphorus (P) based – nanomaterials (NMs) are currently being explored as nano... more Abstract Biogenic phosphorus (P) based – nanomaterials (NMs) are currently being explored as nanofertilizers. In this study, the acute toxic effects and trophic transfer of multiple types of P-based NMs were examined on soil-dwelling nematode, Caenorhabditis elegans. The study involved four variants of nanohydroxyapatites (nHAPs) synthesized either via a biogenic or a chemical route and another NM, nanophosphorus (nP), biosynthesized from bulk rock phosphate (RP). The pristine NMs differed in their physicochemical properties with each possessing different shapes (biogenic nHAP: platelet-shaped, ˜35 nm; biogenic nP, ˜5–10 nm: dots; chemically synthesized nHAPs: spherical, ˜33 nm, rod, ˜80 nm and needle-shaped, ˜64 nm). The toxic effects of NMs' in C. elegans were assessed using survival, hatching and reproductive cycle as the key endpoints in comparison to bulk controls, calcium phosphate and RP. The interactions and potential uptake of fluorescent-tagged nHAP to E. coli OP50 and C. elegans were investigated using confocal microscopy. The transformation of NMs within the nematode gut was also explored using dynamic light scattering and electron microscopy. C. elegans exposed to all of the variants of nHAP and the nP had 88–100% survival and 82–100% hatch rates and insignificant effects on brood size as observed at the tested environmentally relevant concentrations ranging from 5 to 100 μg.mL−1. Confocal microscopy confirmed the interaction and binding of fluorescent-tagged nHAP with the surface of E. coli OP50 and their trophic transfer and internalization into C. elegans. Interestingly, there was only a small reduction in the hydrodynamic diameter of the nHAP after their uptake into C. elegans and the transformed NMs did not induce any additional toxicity as evident by healthy brood sizes after 72 h. This study provides key information about the environmental safety of agriculturally relevant P-based NMs on non-target species.

Research paper thumbnail of In Vitro Assessment of Core-Shell Micellar Nanostructures of Amphiphilic Cationic Polymer-Peptide Conjugates as Efficient Gene and Drug Carriers

Journal of Pharmaceutical Sciences, 2020

Design and development of biocompatible, biodegradable and stable dual delivery systems for drug ... more Design and development of biocompatible, biodegradable and stable dual delivery systems for drug and gene is the need of the hour. Here, we have designed a strategy to develop carrier systems consisting of above mentioned properties by (a) incorporating an unnatural amino acid in the peptide backbone, and b) conjugating a low molecular weight cationic polymer (polyethylenimine, PEI) for incorporating cationic charge. Using this strategy, we have synthesized a small series of Boc-FΔF-AH-polyethylenimine conjugates by varying the concentration of Boc-FΔF-aminohexanoic acid, viz., PP-1, PP-2 and PP-3. These conjugates self-assembled in aqueous medium to form micelles in the size range of ∼144-205 nm with zeta potential ∼ +7.9-14.2 mV bearing core-shell type of conformation. Positive surface of the micelles facilitated the binding of plasmid DNA as well as transportation inside the cells. The hydrophobic core of the nanostructures helped in the encapsulation of the hydrophobic drug molecule, which was then got released in a controlled manner. DNA complexes of the conjugates were not only found non-toxic but also exhibited higher transfection efficacy than the native polymer and Lipofectamine. Altogether, these nanostructures are capable of delivering a drug and a gene simultaneously in vitro and could be used as next-generation delivery agents.

Research paper thumbnail of A new method for biological synthesis of agriculturally relevant nanohydroxyapatite with elucidated effects on soil bacteria

Scientific Reports, 2019

The study describes a novel and environment friendly route of biosynthesis of nanohydroxyapatite ... more The study describes a novel and environment friendly route of biosynthesis of nanohydroxyapatite (nHAP). Bacillus licheniformis mediated synthesis of nHAP has been carried out with different phosphate concentrations (2%, 5%, 10% and 20% w/v) of potassium dihydrogen orthophosphate monobasic (K2HPO4). The synthesis is supported by a two-step mechanism – (i) solubilization of P by organic acids extracellularly secreted by the bacterial strain and (ii) gelation of P and Ca. The nHAP particles were characterized using electron microscopy and XRD analysis. Powdered crystalline particles with a size range of 30 ± 5 nm were obtained with shape and size dependent on phosphate concentrations. The particles showed no adverse effect on plant growth-promoting bacteria. Evaluation of nHAP prepared by this route with 2% P source provides scope for a wide range of applications, especially as a nano-fertilizer.

Research paper thumbnail of Polydopamine –aminoglycoside nanoconjugates: Synthesis, characterization, antimicrobial evaluation and cytocompatibility

Materials Science and Engineering: C, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Iron chelator Deferoxamine protects human neuroblastoma cell line SH-SY5Y from 6-Hydroxydopamine-induced apoptosis and autophagy dysfunction

Journal of Trace Elements in Medicine and Biology, 2019

Background: Intracellular iron involves in Fenton's reaction-mediated Hydroxyl radical (OH•) gene... more Background: Intracellular iron involves in Fenton's reaction-mediated Hydroxyl radical (OH•) generation by reacting with the neurotoxic agent 6-Hydroxydopamine (6-OHDA) autoxidation derivative Hydrogen Peroxide (H 2 O 2). Several studies have been conducted so far on the neuroprotective activities of the iron chelator Deferoxamine (DFO) but little or no clear evidence about the underlying cellular mechanism is available. Methods: The present study was conducted on Human neuroblastoma cell line SH-SY5Y in the absence or presence of 6-OHDA or H 2 O 2 and / or DFO. Following incubation, cell viability assay, intracellular reactive oxygen species (ROS) determination, flow cytometric quantification of apoptotic cells followed by nuclear staining, intracellular tracking of transfected fusion construct of microtubule-associated protein 1B-light chain with Green fluorescent protein-Red fluorescent protein (LC3B-GFP-RFP reporters) and immunocytochemistry of intracellular Cathepsin protein by confocal microscopy, were conducted. In addition, western blotting was carried out to detect expressions of apoptotic and autophagy related proteins. Results: This study confirmed the neuroprotective potential of DFO by inhibiting 6-OHDA-mediated cell death and ROS generation. Reduced percentage of apoptotic cells and appearance of altered nuclei architecture followed by a reduced expression of cleaved PARP (Poly-ADP-ribose Polymerase) and cleaved Caspase-3 were observed upon DFO treatment against 6-OHDA, and as well as against H 2 O 2 in SH-SY5Y cell lines. Besides, DFO induced the intracellular autophagolysosome formation (red puncta) rather than autophagosome (yellow puncta) only. Thereafter it was observed that DFO restored the expression of intracellular lysosomal protease Cathepsin and reduced the expression of the LC3-II. Conclusion: Taken together, this study clearly demonstrated that the anti-Fenton activity of DFO inhibited apoptosis and caused blockade in ALP or autophagy dysfunction in SH-SY5Y cell lines. These outcomes further suggest that DFO provides neuroprotection by inhibiting apoptosis and inducing the progression of Autophagylysosomal pathway (ALP).

Research paper thumbnail of Enhanced solubility and self-assembly of amphiphilic sulfasalazine-PEG-OMe (S-PEG) conjugate into core-shell nanostructures useful for colonic drug delivery

Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2018

Recently, several studies have been undertaken to formulate drugs in soluble state leading to enh... more Recently, several studies have been undertaken to formulate drugs in soluble state leading to enhanced bioavailability as well as to provide controlled drug release. Because of their distinct advantages, such systems have attracted increasing attention of the researchers. Here, sulfasalazine, a drug used to treat inflammatory bowel disease, was conjugated with a low molecular weight polyethylene glycol monomethyl ether (750 Da) to obtain amphiphilic sulfasalazine-polyethylene glycol (S-PEG) conjugate, which not only showed enhanced solubility but also, on self-assembly, generated core-shell type micellar nanostructures with hydrophobic core and hydrophilic shell. Post-physicochemical characterization, these micellar nanostructures were used to entrap hydrophobic drug molecules, ornidazole and sulfasalazine. The drug-entrapped S-PEG nanoformulations showed controlled release of drugs at pH 7.2 making these nanoformulations ideal for colon-targeted drug delivery. Further, azo-moiety bearing sulfasalazine conjugate showed responsiveness to a chemical reductant, sodium dithionite, which mimics azoreductase enzymes present in the colonic microflora. Drug release in the presence of sodium dithionite increased significantly ensuring the potential of these formulations for colon-targeted drug delivery.

Research paper thumbnail of Understanding the safety aspect of biologically synthesized agriculturally useful nanomaterials for humans and environment

Frontiers in Nanoscience and Nanotechnology, 2018

Research paper thumbnail of Role of Endocrine-Disrupting Engineered Nanomaterials in the Pathogenesis of Type 2 Diabetes Mellitus

Frontiers in Endocrinology, 2018

Keywords: engineered nanomaterial (ENM), type 2 diabetes mellitus (T2DM), endocrine disruptor, in... more Keywords: engineered nanomaterial (ENM), type 2 diabetes mellitus (T2DM), endocrine disruptor, insulin resistance, reduced insulin sensitivity, oxidative stress, in vitro and in vivo studies, epidemiological evidences BACKGROUND Materials acquire unique characteristics when the size of the particle is reduced to nanoscale. Nanomaterials (NMs) are a universal set of nanoscale materials having at least one of the dimensions in the nano-range. With having at least one dimension in nanoscale as a common feature, nanoparticles, nanowires, nanosheets, nanotubes, and nanoplates can be stated as the key subsets of NMs (1). The various properties of a nanomaterial (NM), including its melting point, electrical conductivity, magnetic permeability, chemical reactivity and fluorescence, are determined by the particle size (2). Sizereduction of a material to nanoscale enhances its functional aspects and associated technological benefits. Therefore, the use of engineered nanomaterials (ENMs) in the development of advanced technologies for medicine, engineering and natural sciences has significantly increased since the start of the twentyfirst century (3). ENMs are being incorporated into our everyday routine as a part of clothing, food, cosmetics, medicines,

Research paper thumbnail of Mussel-inspired polydopamine-polyethylenimine conjugated nanoparticles as efficient gene delivery vectors for mammalian cells

Colloids and surfaces. B, Biointerfaces, Jan 26, 2017

Efficient delivery of DNA to cells is the primary concern to address the objective of gene therap... more Efficient delivery of DNA to cells is the primary concern to address the objective of gene therapy. Many attempts have been made to develop polymeric carriers for gene delivery. To have an efficient carrier, it is vital to understand the properties of the vector for better stability, transfection efficiency and minimal toxicity. Branched polyethylenimine (bPEI) has been considered as the 'gold standard' for gene delivery but suffers a major drawback of exhibiting high cytotoxicity. Here, we have attempted to develop a mussel-derived polymer, polydopamine (PDA), conjugated polyethylenimine nanoparticles in such a way that the toxic nature of bPEI is suppressed by the conversion of free primary amine groups to secondary and tertiary amines. Keeping the amount of PDA fixed, varying amounts of bPEIs of different molecular weights (25, 10 and 1.8kDa) were conjugated via Michael addition and/or Schiff base. A trend in hydrodynamic size of the conjugated nanoparticles was observed ...

Research paper thumbnail of Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole

International journal of biological macromolecules, Jan 14, 2017

Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompat... more Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, a unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the h...

Research paper thumbnail of Ligands with Delocalized Charge Density and Hydrophobicity Significantly Affect the Transfection Efficacy of the PAMAM Dendrimer

Pharmaceutical Nanotechnology, 2015

Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic aci... more Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic acids to the cells. However, these dendrimers cause a significant amount of cytotoxicity. In order to improve its transfection efficiency and cell viability, surface amine groups of PAMAM were converted into guanidinium (Gn) and tetramethylguanidi-nium (TMG) moieties. These modified PAMAM dendrimers interacted with negatively charged plasmid DNA efficiently and formed stable complexes as revealed by dynamic light scattering analysis. PAMAM/pDNA, PAMAM-TMG/pDNA and PAMAM-Gn/pDNA complexes were found to be in the range of 175-250 nm with zeta potential in the range of +21-37 mV. Further, these modified dendrimers did not display toxicity rather it decreased a bit when tested in HEK293, HeLa and MCF-7 cells. Among these modified dendrimers, PAMAM-Gn/pDNA complex displayed the highest transfection efficiency in both the cell lines HEK293 and MCF-7.

Research paper thumbnail of Ligands with Delocalized Charge Density and Hydrophobicity Significantly Affect the Transfection Efficacy of the PAMAM Dendrimer

Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic aci... more Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic acids to the cells. However, these dendrimers cause a significant amount of cytotoxicity. In order to improve its transfection efficiency and cell viability, surface amine groups of PAMAM were converted into guanidinium (Gn) and tetramethylguanidi-nium (TMG) moieties. These modified PAMAM dendrimers interacted with negatively charged plasmid DNA efficiently and formed stable complexes as revealed by dynamic light scattering analysis. PAMAM/pDNA, PAMAM-TMG/pDNA and PAMAM-Gn/pDNA complexes were found to be in the range of 175-250 nm with zeta potential in the range of +21-37 mV. Further, these modified dendrimers did not display toxicity rather it decreased a bit when tested in HEK293, HeLa and MCF-7 cells. Among these modified dendrimers, PAMAM-Gn/pDNA complex displayed the highest transfection efficiency in both the cell lines HEK293 and MCF-7.

Research paper thumbnail of Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole

Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompat... more Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486 nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, an unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the hydrophobic core and released 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 been studied. Altogether, small peptide conjugated to inulin offers novel scaffold for the future design of nanostructures with potential applications in the field of targeted drug delivery.