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Cryopreservation of Crassostrea gigas vesicular cells: viability and metabolic activity.

Cryopreservation is widely used for long-term conservation of various tissues, embryos or gametes. However, few studies have described cryopreservation of invertebrate primary cell cultures and more particularly of marine invertebrate somatic cells. This technique would however be of great interest to facilitate the study of various metabolic processes which vary seasonally. The aim of the present study was to develop a protocol for cryopreservation of Crassostrea gigas vesicular cells. Different parameters were adjusted to improve recovery of cells after freezing. The most efficient cryoprotectant agent was a mix of Me(2)SO, glycerol, and ethylene glycol (4% each). The optimal cooling rate was -1 degrees Cmin(-1) down to -70 degrees C before transfer into liquid nitrogen. In these conditions the percentage of viable cells reached 70% of the control. The glucose metabolism of thawed cells was evaluated using radioactive glucose as a tracer. Immediately after thawing, glucose uptake involving membrane transporters was greatly reduced (24% of control) whereas glucose incorporation into glycogen was less affected (68% of control).

Animals↗

Nitrogen budgets for three cropping systems fertilised with cattle manure.

A field plot experiment was set up on a sandy loam soil of SW England in order to determine the efficiency of nitrogen use from different cattle manures. The manure treatments were low and high dry matter cattle slurries and one farmyard manure applied at a target rate of 200 kg total N ha(-1)year(-1), and an untreated control. There were three different cropping systems: ryegrass/clover mixture, maize/rye and maize/bare soil, which were evaluated during 1998/99 and 1999/00. Measurements were made of N losses, N uptake and herbage DM yields. Result showed that manure type had a significant effect on N utilisation only for maize. N balances were negative in maize (approximately -247 to -10 kg N) compared to grass (approximately 5-158 kg N). Agronomic management was more important than manure type in influencing N losses, where soil cultivation appeared to be a key factor when comparing maize and grass systems.

Animals↗

Controlled release urea as a nitrogen source for spring wheat in Western Canada: yield, grain N content, and N use efficiency.

Controlled release nitrogen (N) fertilizers have been commonly used in horticultural applications such as turf grasses and container-grown woody perennials. Agrium, a major N manufacturer in North and South America, is developing a low-cost controlled release urea (CRU) product for use in field crops such as grain corn, canola, wheat, and other small grain cereals. From 1998 to 2000, 11 field trials were conducted across western Canada to determine if seed-placed CRU could maintain crop yields and increase grain N and N use efficiency when compared to the practice of side-banding of urea N fertilizer. CRU was designed to release timely and adequate, but not excessive, amounts of N to the crop. Crop uptake of N from seed-placed CRU was sufficient to provide yields similar to those of side-banded urea N. Grain N concentrations of the CRU treatments were higher, on average, than those from side-banded urea, resulting in 4.2% higher N use efficiency across the entire N application range from 25 to 100 kg ha(-1). Higher levels of removal of N in grain from CRU compared to side-banded urea can result in less residual N remaining in the soil, and limit the possibility of N losses due to denitrification and leaching.

Agriculture↗

Optimizing photoheterotrophic H2 production by Rhodobacter capsulatus upon interposon mutagenesis in the hupL gene.

In Rhodobacter capsulatus, the hupL gene encoding the large subunit of the uptake-hydrogenase (Hup) enzyme complex was mutated by insertion of an interposon. The mutant neither synthesized an active hydrogenase nor grew photoautotrophically. Under conditions of nitrogen (N) limitation, photoheterotrophic cultures of the wild type and the mutant evolved H2 by activity of the nitrogenase enzyme complex. When grown with glutamate as an N source and either D,L-malate or L-lactate as carbon sources, the efficiency of H2 production by the HupL mutant was higher than 90%, whereas wild-type cultures exhibited efficiencies of 54% (with D,L-malate) and 64% (with L-lactate), respectively. With NH4+ as the N source, efficiencies of H2 production were 70% (mutant) and 52% (wild type).

Biotechnology↗

Treatment of strong nitrogen swine wastewater in a full-scale sequencing batch reactor.

Treatment of swine wastewater containing strong nitrogen was attempted in a full-scale SBR. The strongest swine wastewater was discharged from a slurry-type barn and called swine-slurry wastewater (SSW). Slightly weaker wastewater was produced from a scraper-type barn and called swine-urine wastewater (SUW). TCOD, NH4+-N and TSS in raw SSW were 23,000-72,000 mg/L, 3,500-6,000 mg/L and 17,000-50,000 mg/L, respectively. A whole cycle of SBR consists of 4 sub-cycles with anoxic period of 1 hr and aerobic period of 3 hr. The maximum loading rates of both digested-SSW and SUW were similar to 0.22 kg NH4+-N/m3/day whereas the maximum loading rates of raw SSW was up to 0.35 TN/m3/day on keeping the effluent quality of 60 TN mg/l. The VFAs portion of SCOD in raw SSW was about more than 60%. The VFAs in SUW and digested-SSW were about 22% and 15%, respectively. NH4+-N and PO4(3-)-P in SSW were removed efficiently compared to those in digested-SSW and DUW because SSW had high a C/N ratio and readily biodegradable organic. High concentration of organic was useful to enhance denitrification and P uptake. Also the amount of external carbon for denitrification was reduced to 5% and 10% of those for digested-SSW and SUW.

Agriculture↗

Effect of supplementing a fibre basal diet with different nitrogen forms on ruminal fermentation and microbial growth in an in vitro semi-continuous culture system (RUSITEC)

Incubation trials were carried out with the rumen simulation technique (RUSITEC) to study the effects of four forms of N on the growth of ruminal micro-organisms and the fermentation variables when an all-fibre basal diet was incubated. The basal diet consisted of 10 g neutral-detergent fibre (NDF) from grass hay plus 2 g NDF from sugarbeet pulp. N forms were isolated soyabean protein, soyabean peptides, amino acids blended to profile soyabean protein and NH3 as NH4Cl. Half of the daily N supply was infused as NH4Cl and the other half was infused as each of the four treatments described. Non-NH3 N (NAN) forms increased NDF (P = 0.006), acid-detergent fibre (P = 0.003) and cellulose (P = 0.015) disappearance after 48 h incubation, CO2 (P < 0.001), CH4 (P = 0.002) and total volatile fatty acids production (P < 0.001), as well as the molar percentages of isobutyrate, isovalerate and valerate, which reflected the fermentation of amino acid C skeletons. NAN treatments also increased microbial N flow (P < 0.001) compared with NH3, with peptides and protein supporting more (P = 0.036) than amino acids. The proportion of microbial N derived from NH3 decreased successively (P < 0.05) with NH3 > amino acids > peptides > protein treatments, indicating preferential uptake of peptides without passage through the NH3 pool. Microbial efficiency (g microbial N/kg organic matter apparent disappearance) was greater (P = 0.002) for the NAN forms than for the NH3 treatment, with peptides and protein treatments supporting higher (P = 0.009) values than amino acid treatment. These results indicate that N forms other than NH3 are required for optimal fibre digestion and microbial growth.

Ammonia↗

Peptide mixtures for enteral and parenteral nutrition.

This article reviews the work concerning intestinal absorption of amino acids from a mixture of 12 glycyl-dipeptides in human jejunum as well as nutritional efficacy and safety of different dipeptide mixtures as the nitrogen source of total parenteral nutrition in baboons. Using a segmental perfusion technique, amino acid absorption rates were generally greater and less selective from the dipeptide mixture as compared to the corresponding free amino acid mixture. This can only be explained as a result of peptide uptake by a system that has greater transport capacity than amino acid carrier systems, thus minimizing competition among its substrates. To assess the efficacy and safety of dipeptides as substrates for total parenteral nutrition, the effects of intravenous infusion of two different synthetic dipeptide mixtures as well as a dipeptide supplemented free amino acid mixture on a range of parameters of nutrition, metabolism and organ function were investigated. In each experiment the corresponding free amino acid mixtures served as control. In three experiments in baboons with the period of parenteral nutrition being 1 or 4 weeks, respectively, all dipeptides were efficiently utilized, as evidenced by only trace concentrations of dipeptides in plasma and urine. With a dipeptide supplemented amino acid solution as well as with complete dipeptide mixtures serving as the sole source of nitrogen of parenteral solutions, parameters of nutrition, metabolism and organ function were well maintained. No adverse effects of the dipeptides occurred. These experiments provide the information needed for further investigation of dipeptides as a substrate of enteral and parenteral nutrition in man.

Amino Acids↗

Disruption of the uptake hydrogenase gene, but not of the bidirectional hydrogenase gene, leads to enhanced photobiological hydrogen production by the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.

In order to determine the effects of the deletion of hydrogenase genes on nitrogenase-based photobiological H(2) productivity by heterocystous N(2)-fixing cyanobacteria, we have constructed three hydrogenase mutants from Anabaena sp. PCC 7120: hupL(-) (deficient in the uptake hydrogenase), hoxH(-) (deficient in the bidirectional hydrogenase), and hupL(-)/ hoxH(-) (deficient in both genes). The hupL(-) mutant produced H(2) at a rate four to seven times that of the wild-type under optimal conditions. The hoxH(-) mutant produced significantly lower amounts of H(2) and had slightly lower nitrogenase activity than wild-type. H(2) production by the hupL(-)/ hoxH(-) mutant was slightly lower than, but almost equal to, that of the hupL(-) mutant. The efficiency of light energy conversion to H(2) by the hupL(-) mutant at its highest H(2) production stage was 1.2% at an actinic visible light intensity of 10 W/m(2) (PAR) under argon atmosphere. These results indicate that deletion of the hupL gene could be employed as a source for further improvement of H(2) production in a nitrogenase-based photobiological H(2) production system.

Anabaena↗

Using nitrogen-15 to quantify vegetative buffer effectiveness for sequestering nitrogen in runoff.

Previous studies have observed higher levels of soluble nutrients leaving vegetative buffers than entering them, suggesting that the buffers themselves are acting as a source rather than a sink by releasing previously stored nutrients. This study used 98 atom % (15)N-labeled KNO(3) at a rate of 5 kg ha(-1) to quantify buffer efficiency for sequestering new inputs of NO(-)(3)-N in an extensively grazed irrigated pasture system. Buffer treatments consisted of an 8-m buffer, a 16-m buffer, and a nonbuffered control. Regardless of the form of runoff N (NO(-)(3), NH(+)(4), or dissolved organic nitrogen [DON]), more (15)N was lost from the nonbuffered treatments than from the buffered treatments. The majority of the N attenuation was by vegetative uptake. Over the course of the study, the 8-m buffer decreased NO(-)(3)-(15)N load by 28% and the 16-m buffer decreased load by 42%. For NH(+)(4)-(15)N, the decrease was 34 and 48%, and for DON-(15)N, the decrease was 21 and 9%. Although the buffers were effective overall, the majority of the buffer impact occurred in the first four weeks after (15)N application, with the buffered plots attenuating nearly twice as much (15)N as the nonbuffered plots. For the remainder of the study, buffer effect was not as marked; there was a steady release of (15)N, particularly NO(-)(3)- and DON-(15)N, from the buffers into the runoff. This suggests that for buffers to be sustainable for N sequestration there is a need to manage buffer vegetation to maximize N demand and retention.

Adsorption↗

Simulating nitrogen dynamics in agricultural soils fertilized with pig slurry and urea.

Within the framework of an interregional project in the Emilia Romagna region of northern Italy, the coupled MACRO-SOILN model was chosen to estimate soil protective capacity against pollutants. The aim of our study was to evaluate the model to better identify key parameters and processes that influence N losses in agricultural soils. Nitrate N content was monitored in soil under corn (Zea mays L.) fertilized with urea and/or pig slurry, in two field experiments performed on four different soils: a Fienili clay, a Barco-like silt, a Sant'Omobono silt loam, and a La Boaria silty clay soil. Measurements were compared with model predictions. For all soils, nitrate content was underestimated on average by 24 to 88% at lower N rates; it was overestimated by 1 to 104% at higher N rates. The root mean square error (RMSE) was equal to 81.1%. Simulation of crop N uptake and soil water flow, estimation of the ammonia losses at pig slurry spreading, and N transformation parameter setting were considered as possible error sources. The calibration of crop N uptake gave rise to good model efficiency index values. The RMSE for the simulation of soil water content varied between 9.8 and 20.2%. A more accurate setting of the ammonia losses and of the feces transformation parameter values could allow the RMSE for the simulation of soil nitrate content to be reduced by no more than 10 to 15%. It is possible for the model not to include the simulation of processes that could have relevant effects on the soil N dynamics.

Agriculture↗

Influence of nitrogen source on the fermentation of fibre from barley straw and sugarbeet pulp by ruminal micro-organisms in vitro.

Incubations were carried out with a batch culture system to study the effects of different N sources on the fermentation by ruminal micro-organisms from Merino sheep of two fibre substrates derived from feedstuffs that differed in their fermentation rate. The substrates were neutral-detergent fibre (NDF) from barley straw and sugarbeet pulp. N sources were ammonia (NH4Cl) and peptides (Trypticase). Three treatments were made by replacing ammonia-N with peptide-N at levels of 0 (AMMO), 33 (PEPLOW) and 66 % (PEPHIGH) of total N. There were no differences (P>0.05) between treatments in NDF degradation for both the barley straw and the sugarbeet pulp. Peptides increased (P<0.05) total volatile fatty acids daily production for both substrates, with greater values (P<0.001) for PEPHIGH than for PEPLOW for the sugarbeet pulp. The presence of peptides also increased (P<0.05) microbial N synthesis compared with AMMO, with PEPHIGH supporting more growth (P<0.001) than PEPLOW when the sugarbeet pulp NDF was fermented. The presence of peptides increased (P<0.01) the amount of solids-associated micro-organisms (SAM)-N for both the barley straw and the sugarbeet pulp fibres, values in the PEPHIGH treatment being higher (P<0.001) than those in PEPLOW. The proportion of SAM-N in the total microbial N was not affected (P>0.05) by the presence of peptides compared with the AMMO treatment, but values were greater for the PEPHIGH compared with the PEPLOW N source, reaching statistical significance (P<0.05) only for the sugarbeet pulp. For liquid-associated micro-organisms, the AMMO treatment resulted in the greatest (P<0.05) proportion of N derived from ammonia for both substrates, with a further decrease (P<0.01) for the PEPHIGH treatment compared with the PEPLOW for the sugarbeet pulp, indicating preferential uptake of peptides when they were available. Microbial growth efficiency (g microbial N/kg NDF degraded) was not affected (P>0.05) by N source. These results indicate that N forms other than ammonia are needed for maximal growth of fibre-digesting ruminal micro-organisms.

Animal Feed↗

Effects of macrophytes and external carbon sources on nitrate removal from groundwater in constructed wetlands.

Several microcosm wetlands unplanted and planted with five macrophytes (Phragmites australis, Commelina communis, Penniserum purpureum, Ipomoea aquatica, and Pistia stratiotes) were employed to remove nitrate from groundwater at a concentration of 21-47 mg NO3-N/l. In the absence of external carbon, nitrate removal rates ranged from 0.63 to 1.26 g NO3-N/m2/day for planted wetlands. Planted wetlands exhibited significantly greater nitrate removal than unplanted wetlands (P<0.01), indicating that macrophytes are essential to efficient nitrate removal. Additionally, a wetland planted with Penniserum showed consistently higher nitrate removal than those planted with the other four macrophytes, suggesting that macrophytes present species-specific nitrate removal efficiency possibly depending on their ability to produce carbon for denitrification. Although adding external carbon to the influent improved nitrate removal, a significant fraction of the added carbon was lost via microbial oxidation in the wetlands. Planting a wetland with macrophytes with high productivity may be an economic way for removing nitrate from groundwater. According to the harvest result, 4-11% of nitrogen removed by the planted wetland was due to vegetation uptake, and 89-96% was due to denitrification.

Biodegradation, Environmental↗

Identification of a new locus in the Escherichia coli cotransduction gap that represents a new genetic component of the L-asparagine utilization system.

A temperature-sensitive Escherichia coli mutant defective for the ability to utilize L-asparagine as a sole nitrogen source was isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutation (asu) produces two distinct phenotypic effects. Mutant strains grow poorly at high temperature on minimal plates containing asparagine as the sole nitrogen source; this effect is greatly exacerbated by the presence of methionine. Mutant strains utilize L-asparagine as a nitrogen source three to four times more efficiently at permissive temperatures than the wild-type strains. The mutation maps at 32.4 min on the E. coli chromosome, within the E. coli cotransduction gap. Mutant strains produce normal amounts of thermo-stable L-asparaginase I activity. The mutation therefore affects a component of the asparagine utilization system other than the catabolism of asparagine within the cell; it probably affects asparagine uptake.

Asparaginase↗

Root environment acidity as a regulatory factor in ammonium assimilation by the bean plant.

Previous experiments have revealed a much greater efficiency of ammonium utilization by bean plants (Phaseolus vulgaris L.) when the acidity of the ambient medium was maintained at near-neutral conditions with carbonates or hydroxides. The present investigation, in which (15)N-labeled ammonium was used, permitted an assessment of the origin of nitrogen in tissue nitrogen pools with and without acidity control (CaCO(3) treated and untreated, respectively) in the root environment. Control of acidity resulted in greater ammonium uptake and greater incorporation into the amino fraction, amide, and ethanol-insoluble nitrogen by the root tissue. These differences were clearly evident by the fifth day after ammonium nitrogen had been applied.Shoots of the untreated plants rapidly accumulated free ammonium and amino nitrogen. A substantial portion of both fractions came from pre-existing nitrogen in the plants, indicating significant protein degradation. No evidence was found for such degradation in the roots of the untreated plants or in either roots or shoots of CaCO(3) treated plants. The data indicate that control of ambient acidity in the root environment during ammonium absorption enhanced the conversion of entering ammonium to organic nitrogen compounds in the root tissue thereby restricting movement of free ammonium to shoots. Consequently, the detrimental effects of high ammonium concentrations in the leaves were largely prevented.

Journal Article↗

Bacillus megaterium mutant deficient in membrane-bound adenosine triphosphatase activity.

An adenosine triphosphatase (ATPase) mutant of Bacillus megaterium was isolated and characterized. This mutant (designated A37) was unable to grow on nonfermentable carbon sources and possessed less than 5% of the wild-type ATPase activity. Oxygen uptake by the mutant was comparable to that in the wild type. Sporulation in the wild type occurred in both glucose- and nitrogen-limiting media; however, A37 sporulated only in the nitrogen-limiting medium. The inability of A37 to sporulate in glucose-limiting medium seemed to be due to insufficient adenosine 5'-triphosphate (ATP) levels during the sporulation stages. Fructose, which can generate ATP via substrate-level phosphorylation, is equally efficient in stimulating ATP synthesis in the wild type and A37. Malate-stimulated ATP synthesis in the wild type was shown to have many characteristics associated with oxidative phosphorylation and was absent in the mutant. These data suggest that the ATPase deficiency results in the loss of oxidative phosphorylation.

Adenosine Triphosphatases↗

Effect of carbohydrate source on ammonia utilization in lactating dairy cows.

This study was conducted to investigate the effect of dextrose, starch, NDF, and a carbohydrate (CHO) mix on utilization of ruminal ammonia in dairy cows. Four ruminally and duodenally cannulated Holstein cows (BW = 788 +/- 31 kg; 217 +/- 35 d in milk) were allocated to four treatments in a 4 x 4 Latin square design trial. Cows were fed an all alfalfa diet at 12-h intervals (DMI = 22.2 +/- 0.25 kg/d). Treatments were control, white oat fiber (NDF); corn dextrose (GLU); cornstarch (STA); and a CHO mix (25% of each): apple pectin, GLU, STA, and NDF (MIX). Carbohydrates were introduced intraruminally during feeding at 20% of dietary DMI. Ruminal ammonia was labeled with (15)N. Ruminal pH was the highest for NDF followed by STA and MIX and GLU (P < 0.001). Ruminal ammonia concentration and pool size were decreased by GLU and STA compared with NDF (P < 0.001 and P = 0.03, respectively). Acetate, isobutyrate, isovalerate, and total VFA concentration in the rumen were decreased (P = 0.009 to 0.001), and butyrate was increased (P < 0.001) by GLU compared with the other CHO. Microbial N flow to the duodenum was decreased (P < 0.05) by NDF compared with the other CHO, and the flow of microbial N formed from ammonia was greater for STA compared with GLU and NDF (P = 0.04 and 0.03, respectively). Urinary N loss was decreased (P = 0.05) by GLU and STA, but overall (feces plus urine) N losses were not affected (P = 0.73) by treatment. Milk urea concentration was lowered by GLU and STA compared with NDF and MIX (P = 0.002). The proportion of bacterial N synthesized from ammonia in the rumen was greater with STA than with NDF and MIX and was least for GLU (P = 0.02). Irreversible ammonia loss and flux were lower (P = 0.09 and 0.02, respectively) for GLU than for STA and NDF. As a percentage of the dose given, cumulative secretion of (15)N ammonia in milk protein was greater for STA than for GLU or NDF (P = 0.01 and 0.001, respectively). This experiment demonstrated that provision of readily fermentable energy can decrease ammonia concentrations in the rumen through decreased ammonia production (GLU), or through enhanced uptake of ammonia for microbial protein synthesis (STA). Rapidly fermentable energy in the rumen decreased ammonia production and flux, but the overall efficiency of ammonia utilization for milk protein synthesis was only increased by enhancing ruminal microbial ammonia uptake.

Ammonia↗

Remobilization and uptake of N by newly planted apple (Malus domestica) trees in response to irrigation method and timing of N application.

Environmentally sound management of N in apple orchards requires that N supply meets demand. In 1997, newly planted apple trees (Malus domestica Borkh. var. Golden Delicious on M.9 rootstock) received daily applications of N for six weeks as Ca(15NO3)(2) through a drip irrigation system at a concentration of 112 mg l(-1) at 2-8, 5-11 or 8-14 weeks after planting. Irrigation water was applied either to meet estimated evaporative demand or at a fixed rate. In 1997, trees were harvested at 5, 8, 11 and 14 weeks after planting; and in 1998 at 3 weeks after full bloom. The amount of fertilizer N recovered was similar in trees in both irrigation treatments, but efficiency of fertilizer use was greater for trees receiving demand-controlled irrigation than fixed-rate irrigation. This was attributed to lower N inputs, greater retention time in the root zone and less N leaching in the demand-controlled irrigation treatments compared with fixed-rate irrigation treatments. Less fertilizer N was recovered by trees receiving an early application of N than a later application of N and this was related to the timing of N supply with respect to tree demand. Demand for root-supplied N was low until 11 weeks after planting, because early shoot and root growth was supported by N remobilized from woody tissue, which involved 55% of the total tree N content at planting. Rapid development of roots > 1 mm in diameter occurred between 11 and 14 weeks after planting, after remobilization ended, and was greater for trees receiving an early application of N than for trees receiving a later application of N. Late-season tree N demand was supplied by native soil N, and uptake and background soil solution N concentrations were higher for trees receiving demand-supplied irrigation compared with fixed-rate irrigation. Total annual N uptake by roots was unaffected by treatments and averaged 6-8 g tree(-1). Nitrogen applications in 1997 affected growth and N partitioning in 1998. Trees receiving early applications of N had more flowers, spur leaves and bourse shoots than trees receiving later applications of N. Consequently, more N was remobilized into fruits in trees receiving early applications of N compared with fruits in trees receiving later applications of N. Demand for N in the young apple trees was low. Early season demand was met by remobilization from woody tissues and the timing of demand for root-supplied N probably depends on whether flowering occurs. Method of N delivery affected the efficiency of N use. We conclude that N demand can be met at soil solution N concentrations of around 20 mg l(-1).

Agriculture↗

Targeted delivery of arjunglucoside I using surface hydrophilic and hydrophobic nanocarriers to combat experimental leishmaniasis.

The purpose of the present study was to investigate the therapeutic efficacy of the indigenous drug arjunglucoside I (AG) against in vivo models of experimental leishmaniasis by incorporating it in surface hydrophilic co-polymeric nanogel particles of size less than 100 nm diameter and to compare its efficacy with that of the free drug as well as the drug encapsulated in hydrophobic poly-dl-lactide (PLA) nanoparticles. The drug AG, having glucose at the terminal end of the glycosidic chain, was isolated from an indigenous source. Drug-incorporated ultra-low-sized nanogels (approximately 90 nm in diameter) composed of cross-linked random co-polymer of N-isopropylacrylamide (NIPAAM) and N-vinyl pyrrolidone(VP) were prepared, characterized and used as delivery vehicles to combat experimental leishmaniasis in hamster models. For comparison, drug-encapsulated hydrophobic nanoparticles (approximately 250 nm in diameter) made from PLA were used as a control. The drug AG was incorporated in these nanocarriers and these drug-nanocarrier complexes were physically characterized. The efficacy of lowering spleen parasite load by the free drug, as well as that incorporated in nanogels and PLA nanoparticles were examined in vivo in equimolar concentration against hamsters undergoing experimental leishmaniasis. The reduction of drug toxicity by the nanogels and PLA nanoparticles was also assessed. The efficacy in the lowering of spleen parasite load with the free drug was found to be only 38% but was much higher when the drug was incorporated in co-polymeric nanogels (79%) or in polymeric nanoparticles (75%). Both the nanocarriers were found to be effective in reducing hepatotoxicity and nephrotoxicity nearly to the same extent. It was apparent that in addition to a smaller size and better drug release profile, the contribution of other parameters, e.g. overall surface hydrophilicity or hydrophobicity of the vehicles, also play an important role in the macrophage uptake of the drug. However, whatever be the exact mechanism, being highly efficient, non-hepatotoxic and non-nephrotoxic, AG in either of the two nanoparticulate forms may have useful application in humans

Animals↗