Bakul Kumar Datta

Development of New Localized Drug Delivery System Based on Ceftriaxone-Sulbactam Composite Drug Impregnated Porous Hydroxyapatite: A Systematic Approach for In Vitro and In Vivo Animal Trial

ABSTRACTPurposePresent investigation deals with an extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis, using hydroxyapatite porous scaffolds.Materials and MethodsHydroxyapatite was synthesized in the laboratory by wet chemical method, different porous scaffolds have been fabricated. In vitro studies include variation of porosity with interconnectivity, pore-drug interfacial studies by SEM-EDAX and drug elution studies (by HPLC) both in contact with PBS and SBF at ~37°C. In vivo trials were based on experimental osteomyelitis in rabbit model induced in tibia by Staphylococcus aureus. Characterizations included observation of histopathology, radiology and estimation of drug in both bone and serum for 42 days by HPLC method and subsequent bone-biomaterial interface by SEM.ResultsIt was established that lower pore percentage with a distribution of mainly micro-pores were found to be superior over the higher pore percentage both in vitro and in vivo. The criteria was matched with the 50N50H samples which had 50–55% porosity with an average pore size ~110 μm, having higher interconnectivity (10–100 μm), moderately high adsorption efficiency (~50%) when loaded with CFS (drug combinations consisting of irreversible b-lactamase inhibitor and b-lactam antibiotic). CFS release from HAp implants were faster in PBS than SBF. Further, both the results of in vitro and in vivo drug elution after 42 days showed release higher than minimum inhibitory concentration of CFS against Staphylococcus aureus. In vivo studies also proved the superiority of CFS loaded HAp implants than parenteral group based on eradication of infection and new bone formation.ConclusionsHAp based porous scaffold loaded with CFS and designed porosity (in terms of micro- and macro-porosity, interconnectivity) was found to be an ideal delivery system which could locally, sustainably release the composite antibiotic in reliable manner both in terms of in vitro drug elution behaviour in contact with SBF and in vivo animal trial.

Chronic arsenicosis in cattle with special reference to its metabolism in arsenic endemic village of Nadia district West Bengal India

Thirty Milch cattle were selected randomly from a village of Nadia district of West Bengal, India containing high arsenic in water and soil samples. Milk, feces and hair samples were collected to analyze arsenic status in animals. Water and straw samples were also estimated for arsenic. Milk products prepared from milk of cattle rearing in arsenic prone village were also collected to quantify total arsenic and speciation of arsenic in milk and feces samples were also carried out. It was observed that high amount of arsenic was present in milk, feces, hair of cattle and water and straw samples in arsenic prone village. Milk product also contained significant amount of arsenic than that of milk product of control village. Speciation study revealed arsenite fraction was mainly eliminated through milk, whereas organoarsenic species were mainly excreted through feces.

Quantitative imaging of arsenic and its species in goat following long term oral exposure

Severity of arsenic toxicity was reported to vary depending on its species. The present study reflects the status of different species of arsenic in goat following long-term exposure of arsenic leading to hepatic damage. The experiment was conducted with six black Bengal goats, which were administered with sodium arsenite orally at a dose rate of 2 mgkg(-1) daily for 84 days. Faeces, urine, hair and blood samples were collected from those animals at 14 days interval. Excretion of total arsenic was reduced from 56 days onwards through both faeces and urine indicating higher accumulation of arsenic in body. The speciation study revealed that urinary arsenic was mainly of organic type, whereas hair accumulated almost equal proportion of arsenite, arsenate and organo arsenicals. Goats excreted high proportion of organo arsenicals through faeces possibly due to hepatobiliary secretion of organo arsenic into the gut. Significantly elevated serum alanine aminotransferase and aspartate aminotransferase activities (p<0.05) along with histopathological changes in liver indicated hepatotoxicity. The arsenite fraction increased and organic proportion decreased in urine as the time progressed, which indicates that arsenite gets methylated in liver of goat. The study thus alluded that the toxicity of arsenic would aggravate if the animals were exposed for long time as the hepatotoxicity progressed resulting in decreased methylation and formation of organo arsenicals and decreased excretions through urine.

Effect of environmental exposure of arsenic on cattle and poultry in Nadia district, West Bengal, India

A study was undertaken to evaluate an alternative source of arsenicosis in human food chain through livestock. Thirty milch cattle and 20 poultry birds along with their eggs were selected randomly from two endemic villages of Nadia district and one nonendemic villages of Hooghly district in West Bengal, India. Milk, feces, urine, and hair samples of cattle and feed materials, such as water and straw, were collected to analyze arsenic status. Arsenic concentration in egg yolk and albumen from poultry eggs and different poultry organs after culling was estimated. Distribution of arsenic in animal body indicates that major portion of arsenic was eliminated through feces, urine, and milk. Poultry egg yolk, albumen, and poultry products retain arsenic in all organs. Cows and poultry birds reared in endemic zone retain significantly higher concentration of arsenic. Consumption of egg, agricultural produces grown in contaminated soil, and milk might have produced arsenicosis and may be considered as alternative source of arsenic contamination.

Chronic arsenicosis in cattle: possible mitigation with Zn and Se.

Supply of arsenic free water in the arsenic endemic zone of West Bengal since a long time could not prevent arsenicosis in human completely. So exploration of arsenic contamination at all levels of food chain may be important. The report on arsenicosis in cattle of arsenic affected zone is scarcely available. In the present study, cattle from villages of two arsenic endemic blocks (Chakdah and Haringhata) in Nadia district of West Bengal were selected. The cattle affected with arsenicosis were identified and isolated. They were divided into two groups: untreated control group and treated group-was treated with mixture of zinc oxide (10mg/kg) and sodium selenite (0.1mg/kg) orally once daily for 180 days. Milk, faeces and hair samples were collected at different time intervals from those cattle for analysis of arsenic. Drinking water and straw of those areas were also collected for analysis of arsenic. Serum ALT and AST were estimated in collected blood samples of the cattle. The untreated control group had shown gradual accumulation of total arsenic in hair while the treated group showed a non-significant but declined accumulation of arsenic in hair from 90th day onwards and a significant increase (p<0.05) in total arsenic in faeces from 90th day onwards. The arsenic load considerably but non-significantly decreased in milk from 60th day onwards in the treated group. Serum AST and ALT activities were also decreased in treated cattle. It is concluded that straw is also a major source of arsenic contamination in cattle apart from drinking water and arsenic may enter into human through consumption of contaminated milk. But zinc and selenium mixture may be used to reduce arsenic load in cattle.

Effect of Process Variations on Anticancerous Drug Intercalation in Ceramic Based Delivery System

Two methods have been attempted to intercalate an anionic anticancerous drug methotrexate (MTX) into Mg-Al layered double hydroxide (LDH): a) anion exchange method (sample A′) and b) in situ coprecipitation method followed by a soft hydrothermal treatment (sample A″) to form a biohybrid material. Both the materials obtained were characterized by powdered sample X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), thermogravimetric-differential thermal analysis (TG-DTA), particle size distribution (PSD) analysis and field emission scanning electron microscopy (FE-SEM). High performance liquid chromatography (HPLC) was used to determine the integrity of the MTX and to quantify the drug loading in the materials. HPLC data of sample A′ confirms the integrity of the MTX moiety in the interlayer space of Mg-Al-LDH which has been further verified by XRD and FTIR spectroscopy and drug loading in the hybrid system was found to be 20.22 mg.g−1. However, the HPLC data of sample A″ supports that under soft hydrothermal condition decomposition of MTX is operating and the major decomposition product was identified as N10-methyl folic acid that remains adsorbed on Mg-Al-LDH surface, primarily, as indicated by the TG-DTA study.

Chronic Arsenicosis of Cattle in West Bengal and It's Possible Mitigation by Sodium Thiosulfate.

Thirty milch cows having arsenic concentration in hair varying from 3 to 4 mg/kg from Dakhin Panchpota village of Nadia district, West Bengal, were divided into three equal groups where high amount of arsenic is reported to be present in soil and ground water. Groups II and III received, respectively, sodium thiosulfate 20 and 40 g to each animal for 30 days as a pilot study, whereas group I served as untreated control. Arsenic content of milk, feces, hair, and urine was estimated before and after administration of sodium thiosulfate orally at two dose level once daily for 1 month. Paddy straw, mustard oil cake, and water fed by animals were also assayed. Sodium thiosulfate significantly decreased arsenic load in milk, urine, and hair after 1 month. In milk, arsenic concentration was decreased significantly which may be beneficial for animal and human beings.

Toxicokinetics and recovery studies of dicamba dimethyl amine salt in goats following single oral administration

BACKGROUND Toxicokinetics and recovery studies of dicamba dimethyl amine salt (DDAS) were conducted to obtain more information about its toxicity and tissue retention in farm animals. RESULTS The minimum oral toxic dose level of DDAS was determined as 1400 mg kg(-1) body weight. In the toxicokinetic study, blood DDAS concentration of 55.6 +/- 0.59 microg mL(-1) (mean +/- standard error) was detected at 0.08 h, which peaked to 102.3 +/- 5.03 microg mL(-1) at 0.25 h, and declined to a minimum of 4.1 +/- 0.06 microg mL(-1) at 36 h. In recovery studies, DDAS concentration in urine began to increase significantly (P < 0.05) from 12 h, peaked at 24 h and declined from 48 h onwards. Maximum excretion through faeces was at 24 h and was complete by 144 h. The residual level in tissues decreased significantly (P < 0.05) on day 7 as compared to day 4. In histopathological studies, cellular alterations in lungs, liver, kidney, adrenal gland and spleen were found. CONCLUSION DDAS persists in the body for a shorter period and its major excretory route is through urine. DDAS has lower affinity to accumulate in tissues, and intensity of cellular alterations is not severe after single-dose oral administration.

Chronic Arsenicosis Induced Oxidative Stress in Cattle: Role of Zn and Se

High levels of arsenic in the ground water are a matter of concern, especially in the Indo-Bangladesh region where over a million people are reported to be suffering from arsenic poisoning. This kind of slow, low level, inevitable poisoning has caused serious concerns about the health of all living species in these areas (Majumder et al., 2012).

Hematobiochemical, immunological, antioxidant status, and residues of flumethrin following weekly dermal application in goats

Flumethrin is used extensively in livestock periodically, which may cause adverse effect in goats and subsequently to human being through food chain. Flumethrin at 1.0% solution was applied weekly dermally for 84 days and hematobiochemical as well as immunological parameters, anti-oxidant status, liver enzymes, and tissue residues in goats were estimated. Flumethrin did not produce changes in hemogram except decreased total leukocyte count. Serum protein level was decreased, but serum AST and ALT activities were increased at the end of the study period. IgG level was decreased from the last 2 weeks. But flumethrin did not produce any effect on antioxidant status, as evident from nonsignificant changes in catalase, lipid peroxidation, superoxide dismutase, and reduced glutathione level in liver. Liver AST and ALT activities increased and cytochrome P450 content decreased on day 85. Histopathological study revealed mild changes in liver. Low level of residues of flumethrin was detected in vital tissues following high-performance liquid chromatographic (HPLC) analysis. Flumethrin could not be detected in tissues after 21 days withdrawal period. It may be concluded that flumethrin produces mild changes in various biochemical and immunological parameters from the last 2 weeks of study period and did not have a tendency to accumulate in the different tissues following weekly dermal application for 3 months.