The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral ... more The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.
Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excelle... more Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excellent cytotoxicity against A549 (lung), MCF7 (breast), and HeLa (cervix) cancer cell lines with IC50 values in the range of 0.14–8.59 μM.
The oral route is the most convenient route of drug administration and almost 80 % of the drugs a... more The oral route is the most convenient route of drug administration and almost 80 % of the drugs are administered through this route. Despite many advantages like self-administrable, convenient, economic, pain-free, non-invasive, etc, the oral route is a major challenge for drugs which has low permeability through the GI tract leading to absorption of only 3-10% of the administered dose and reduced bioavailability. Therefore, due to limited half-life (~30 mins) in the stomach and small intestine, to achieve effective response excess of drugs need to be administrated through an oral route which causes many side effects including irritable bowel syndrome, hemorrhoids, gastrointestinal ulcers, and cancer, Cohn's disease, ulcerative colitis, etc. Besides mixing of the un-metabolized drug to the environment like soil and drinking water causes bio-magnifications and infer the development of antibiotic resistance in microorganisms. Therefore, an increase of half-life in the GI tract wou...
Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary dr... more Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of ...
Journal of Photochemistry and Photobiology A: Chemistry
Abstract A novel Schiff base having terephthaldehyde appended with two rhodamine units has been s... more Abstract A novel Schiff base having terephthaldehyde appended with two rhodamine units has been synthesized, which exhibited fluorogenic and chromogenic response on binding with Al3+ ions in 100% aqueous system at pH 7.04. The binding of compound 1 with Al3+ ions was not hindered by the presence of background metal ions. The co-ordination mode of compound 1 was established by Job’s plot method that has been found to be 1:1 stoichiometry with Al3+ ions. The compound 1 could detect Al3+ as low as 1.68 μM in a pH range of 6-10. NMR and mass spectrometry analysis revealed that the Al3+ induced hydrolysis occurs on one side of the Schiff base and led to the formation of free CHO group. The hydrolysed ensemble (1.Al3+) was used for detection of CN− ions (H2O-HEPES buffer, pH 7.04), accompanied by colorimetric and fluorimetric changes. Compound 1 was used to detect Al3+ ions in A549 cells through live cell imaging technique.
ABSTRACTTargeted delivery has not been achieved for anthelmintic treatment, resulting in the requ... more ABSTRACTTargeted delivery has not been achieved for anthelmintic treatment, resulting in the requirement of excess drugs dose leading to side effects and therapeutic resistance. Gastrointestinal helminths ingest lipid droplets from digestive fluid for energy production, development, and defense. Worm’s habit inspired us to develop biocompatible, oral administrable, bee-wax derived solid lipid nanoparticles (SLN) with excellent drug (albendazole) loading efficiency of 83.3 ± 6.5 mg/g and sustained-release properties (86.4 ± 3.9 % of drug released within 24 h). Rhodamine B-loaded SLN showed time-dependent release and distribution of dye in vivo in Haemonchous contortus. The intestinal sustained-release property was shown by the particles that caused enhancement of albendazole potency for up to 50 folds. Therefore, this formulation has immense potential as an anthelminthic drug delivery vehicle that will not only be able to reduce the dose but will also reduce the drug-induced side eff...
Here we show the novel anti-helminthic potential ofLansium parasiticumaqueous extract-protected s... more Here we show the novel anti-helminthic potential ofLansium parasiticumaqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasiteHaemonchus contortus. LAgNPs showed LD50values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metaboli...
Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth suppor... more Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI a...
Four hundred and twenty-two million people have diabetes due to excess free body glucose in their... more Four hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-ɑ, IFN-ϒ, IL-1β and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkβP50/P65 assembly. Insulin shifts the equilibrium towards NFkβP50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation ca...
The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral ... more The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.
Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excelle... more Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excellent cytotoxicity against A549 (lung), MCF7 (breast), and HeLa (cervix) cancer cell lines with IC50 values in the range of 0.14–8.59 μM.
The oral route is the most convenient route of drug administration and almost 80 % of the drugs a... more The oral route is the most convenient route of drug administration and almost 80 % of the drugs are administered through this route. Despite many advantages like self-administrable, convenient, economic, pain-free, non-invasive, etc, the oral route is a major challenge for drugs which has low permeability through the GI tract leading to absorption of only 3-10% of the administered dose and reduced bioavailability. Therefore, due to limited half-life (~30 mins) in the stomach and small intestine, to achieve effective response excess of drugs need to be administrated through an oral route which causes many side effects including irritable bowel syndrome, hemorrhoids, gastrointestinal ulcers, and cancer, Cohn's disease, ulcerative colitis, etc. Besides mixing of the un-metabolized drug to the environment like soil and drinking water causes bio-magnifications and infer the development of antibiotic resistance in microorganisms. Therefore, an increase of half-life in the GI tract wou...
Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary dr... more Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of ...
Journal of Photochemistry and Photobiology A: Chemistry
Abstract A novel Schiff base having terephthaldehyde appended with two rhodamine units has been s... more Abstract A novel Schiff base having terephthaldehyde appended with two rhodamine units has been synthesized, which exhibited fluorogenic and chromogenic response on binding with Al3+ ions in 100% aqueous system at pH 7.04. The binding of compound 1 with Al3+ ions was not hindered by the presence of background metal ions. The co-ordination mode of compound 1 was established by Job’s plot method that has been found to be 1:1 stoichiometry with Al3+ ions. The compound 1 could detect Al3+ as low as 1.68 μM in a pH range of 6-10. NMR and mass spectrometry analysis revealed that the Al3+ induced hydrolysis occurs on one side of the Schiff base and led to the formation of free CHO group. The hydrolysed ensemble (1.Al3+) was used for detection of CN− ions (H2O-HEPES buffer, pH 7.04), accompanied by colorimetric and fluorimetric changes. Compound 1 was used to detect Al3+ ions in A549 cells through live cell imaging technique.
ABSTRACTTargeted delivery has not been achieved for anthelmintic treatment, resulting in the requ... more ABSTRACTTargeted delivery has not been achieved for anthelmintic treatment, resulting in the requirement of excess drugs dose leading to side effects and therapeutic resistance. Gastrointestinal helminths ingest lipid droplets from digestive fluid for energy production, development, and defense. Worm’s habit inspired us to develop biocompatible, oral administrable, bee-wax derived solid lipid nanoparticles (SLN) with excellent drug (albendazole) loading efficiency of 83.3 ± 6.5 mg/g and sustained-release properties (86.4 ± 3.9 % of drug released within 24 h). Rhodamine B-loaded SLN showed time-dependent release and distribution of dye in vivo in Haemonchous contortus. The intestinal sustained-release property was shown by the particles that caused enhancement of albendazole potency for up to 50 folds. Therefore, this formulation has immense potential as an anthelminthic drug delivery vehicle that will not only be able to reduce the dose but will also reduce the drug-induced side eff...
Here we show the novel anti-helminthic potential ofLansium parasiticumaqueous extract-protected s... more Here we show the novel anti-helminthic potential ofLansium parasiticumaqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasiteHaemonchus contortus. LAgNPs showed LD50values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metaboli...
Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth suppor... more Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI a...
Four hundred and twenty-two million people have diabetes due to excess free body glucose in their... more Four hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-ɑ, IFN-ϒ, IL-1β and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkβP50/P65 assembly. Insulin shifts the equilibrium towards NFkβP50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation ca...
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