Physicochemical and pharmacotechnical characterization of Prussian blue for future Prussian blue oral dosage forms formulation.

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient. The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

Enhancing oral bioavailability of Ca-DTPA by self double emulsifying drug delivery system (SDEDDS).

OBJECTIVE: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs. METHODS: SDEDDS formulation was successfully developed using excipients, that is, medium chain triglycerides, oleic acid, phospholipids, Span 80, Tween 80 using double emulsification technique. RESULTS: The optimized formulation F4 (Aq. phase: 11.6%w,w; MCT & oleic acid: 70.9%w/w; Span 80:17.5%w/w; Lecithin:16%w/w and Tween 80 (10%w/w)) appeared bright yellow liquid which upon dilution appeared milky white within 2 min, droplet size (501.7 nm), pdi value (0.044), zeta potential (-52 mV), entrapment efficiency (79.6 ± 1.63), viscosity (72.2 ± 1.8 mpA.s), significant high cumulative in vitro drug permeation (CDP) and 2.17-fold increase in apparent permeability coefficient. Pharmacokinetic studies in rats showed 1.17-fold increases in AUC of F4 and comparatively higher plasma levels (Cmax) compared with pure drug administered orally. The Absolute (OF4, OD) and Relative bioavailability was found to be 14.52%, 12.35%, and 117.47%, respectively. CONCLUSION: The present studies have clearly demonstrated that SDEDDS could readily form w/o/w double emulsions in vivo with enhanced in vitro and in vivo oral bioavailability. Therefore, considerable augmentation in the rate and extent of oral drug absorption ratified the better performance of the SDEDDS in enhancing the bioavailability of Ca-DTPA.

Perilla frutescens: A new strategy for uranium decorporation.

Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa3-DTPA (CaNa3-diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation.

Modelling DTPA therapy following Am contamination in rats.

A major challenge in modelling the decorporation of actinides (An), such as americium (Am), with DTPA (diethylenetriaminepentaacetic acid) is the fact that standard biokinetic models become inadequate for assessing radionuclide intake and estimating the resulting dose, as DTPA perturbs the regular biokinetics of the radionuclide. At present, most attempts existing in the literature are empirical and developed mainly for the interpretation of one or a limited number of specific incorporation cases. Recently, several approaches have been presented with the aim of developing a generic model, one of which reported the unperturbed biokinetics of plutonium (Pu), the chelation process and the behaviour of the chelated compound An-DTPA with a single model structure. The aim of the approach described in this present work is the development of a generic model that is able to describe the biokinetics of Am, DTPA and the chelate Am-DTPA simultaneously. Since accidental intakes in humans present many unknowns and large uncertainties, data from controlled studies in animals were used. In these studies, different amounts of DTPA were administered at different times after contamination with known quantities of Am. To account for the enhancement of faecal excretion and reduction in liver retention, DTPA is assumed to chelate Am not only in extracellular fluids, but also in hepatocytes. A good agreement was found between the predictions of the proposed model and the experimental results for urinary and faecal excretion and accumulation and retention in the liver. However, the decorporation from the skeletal compartment could not be reproduced satisfactorily under these simple assumptions.

Self-Aggregated Nanoscale Metal-Organic Framework for Targeted Pulmonary Decorporation of Uranium.

The limited availability of effective agents for removing actinides from the lungs significantly restricts the effectiveness of medical treatments for nuclear emergencies. Inhalation is the primary route of internal contamination in 44.3% of actinide-related accidents, leading to the accumulation of radionuclides in the lungs and resulting in infections and potential tumor formation (tumorigenesis). This study focuses on the synthesis of a nanometal-organic framework (nMOF) material called ZIF-71-COOH, which is achieved by post-synthetic carboxyl functionalization of ZIF-71. The material demonstrates high and selective adsorption of uranyl, while also exhibiting increased particle size (≈2100 nm) when it aggregates in the blood, enabling passive targeting of the lungs through mechanical filtration. This unique property facilitates the rapid enrichment and selective recognition of uranyl, making nano ZIF-71-COOH highly effective in removing uranyl from the lungs. The findings of this study highlight the potential of self-aggregated nMOFs as a promising drug delivery system for targeted uranium decorporation in the lungs.

Chelation therapy with 3,4,3-Li(1,2-HOPO) after pulmonary exposure to plutonium in rats.

Internal exposure to plutonium can occur through inhalation for the nuclear worker, but also for the public if the radionuclide was released into the atmosphere in the context of a nuclear accident or terrorist attack. DieThylenetriaminePentaAcetic acid (DTPA) is currently still the only authorized chelator that can be used to decorporate internalized plutonium. The Linear HydrOxyPyridinOne-based ligand named 3,4,3-Li(1,2-HOPO) remains the most promising drug candidate to replace it in the hopes of improving chelating treatment. This study aimed to assess the efficacy of 3,4,3-Li(1,2-HOPO) in removing plutonium from rats exposed to the lungs, depending on the timing and route of treatment, and almost always compared to DTPA at a ten-fold higher dose used as a reference chelator. First, early intravenous injection or inhalation of 3,4,3-Li(1,2-HOPO) demonstrated superior efficacy over DTPA in preventing plutonium accumulation in liver and bone in rats exposed by injection or lung intubation. However, this superiority of 3,4,3-Li(1,2-HOPO) was much less pronounced with delayed treatment. In rats given plutonium in the lungs, the experiments also showed that 3,4,3-Li-HOPO reduced pulmonary retention of plutonium more effectively than DTPA only when the chelators were injected early but not at delayed times, while it was always the better of the two chelators when they were inhaled. Under our experimental conditions, the rapid oral administration of 3,4,3-Li(1,2-HOPO) was successful in preventing systemic accumulation of plutonium, but not in decreasing lung retention. Thus, after exposure to plutonium by inhalation, the best emergency treatment would be the rapid inhalation of a 3,4,3-Li(1,2-HOPO) aerosol to limit pulmonary retention of plutonium and prevent extrapulmonary deposition of plutonium in target systemic tissues.

Oral formulation of Prussian blue with improved efficacy for prophylactic use against thallium.

OBJECTIVE: The present study is aimed to enhance the efficacy of Insoluble Prussian blue (PB) in the stomach. PB formulation was developed comprising of PB in combination with pH modifying agents particularly magnesium hydroxide, calcium carbonate, sodium carbonate, and sodium bicarbonate. pH profile and the binding efficacy of the final formulation was evaluated in simulated gastric fluid (SGF). METHODS: The capsule formulation was optimized with desired in vitro characteristics. The final formulations (FF1-FF4) were evaluated for drug release, pH profile, and binding efficacy for thallium (Tl). The stability studies were performed in terms of drug assay, Fourier-transformed infrared (FTIR) spectroscopy and Thermo-gravimetric analysis (TGA). The in vivo study was performed in rats to determine the removal efficacy of optimized formulation (FF4) for Tl. RESULTS: The PB formulation consisting of optimized PB granules and pH modifying agents showed a significant increase in the binding efficacy for Tl in SGF at an equilibrium time of 24 h. The Maximum Binding Capacity (MBC) of FF1-FF4 was found to be higher than commercially available Radiogardase®-Cs capsules and PB granules alone in SGF. The blood Tl level in rats treated with FF4 showed three-fold decreases in the level of Tl in the blood (Cmax) and Area under Curve (AUC) as compared to the control. CONCLUSION: The results revealed that the developed oral PB formulation has a significantly higher efficiency of binding Tl at the acidic pH of the stomach thereby reducing its absorption into the systemic circulation. Thus, the optimized formulation of PB with pH-modifying agents is a better drug for prophylactic use in thallium ingestion.

Chelating decorporation agents for internal contamination by actinides: Designs, mechanisms, and advances.

During the wide utilization of the actinides in medicine, energy, military, and other fields, internal contaminations can profoundly endanger human health and public security. Chelating decorporation agents are the most effective therapies to reduce internal contamination that includes radiological and chemical toxicities. This review introduces the structures of chelating decorporation agents including inorganic salts, polyaminocarboxylic acids, peptides, polyphosphonates, siderophores, calixarenes, polyethylenimines, and fullerenes, and highlights ongoing advances in their designs and mechanisms. However, there are still numerous challenges that block their applications including coordination properties, pharmacokinetic properties, oral bioavailability, limited timing of administration, and toxicity. Therefore, additional efforts are needed to push novel decorporation agents with high efficiency and low toxicity for the treatment of internal contamination by actinides.

A reflection on medical treatment of radionuclide-contaminated wounds during medical response to nuclear emergencies / 中国辐射卫生

Radionuclide-contaminated wounds are common in medical response to nuclear emergencies, which have different manifestations in different types of accidents. Medical treatment is the key part of the response. Based on the drill experience gained from medical response to nuclear emergencies, the authors summarize the research advances in radionuclide-contaminated wounds in recent years, mainly involving the biokinetic characteristics, medical response, surgical debridement, and prevention and treatment of internal contamination of radionuclide-contaminated wounds; the authors summarize the key points of technical operations and provide suggestions on improvements in the drills. The authors believe that medical treatment of radionuclide-contaminated wounds requires highly compatible integration of the practical skills from clinical medicine and radiological knowledge; emergency response, surgical debridement, and prevention and treatment of internal contamination all together constitute an integrated rescue and treatment strategy with internal logic correlations. However, targeted improvements are needed to achieve desired effects in the drills.

Folding Dynamics of 3,4,3-LI(1,2-HOPO) in Its Free and Bound State with U4+ Implicated by MD Simulations.

The octadentate hydroxypyridonate ligand 3,4,3-LI(1,2-HOPO) (t-HOPO) shows strong binding affinity with actinide cations and is considered as a promising decorporation agent used to eliminate in vivo actinides, while its dynamics in its unbound and bound states in the condensed phase remain unclear. In this work, by means of MD simulations, the folding dynamics of intact t-HOPO in its neutral (t-HOPO0) and in its deprotonated state (t-HOPO4-) were studied. The results indicated that the deprotonation of t-HOPO in the aqueous phase significantly narrowed the accessible conformational space under the simulated conditions, and it was prepared in a conformation that could conveniently clamp the cations. The simulation of UIV-t-HOPO showed that the tetravalent uranium ion was deca-coordinated with eight ligating O atoms from the t-HOPO4- ligand, and two from aqua ligands. The strong electrostatic interaction between the U4+ ion and t-HOPO4- further diminished the flexibility of t-HOPO4- and confined it in a limited conformational space. The strong interaction between the U4+ ion and t-HOPO4- was also implicated in the shortened residence time of water molecules.

Boosting Simultaneous Uranium Decorporation and Reactive Oxygen Species Scavenging Efficiency by Lacunary Polyoxometalates.

The chemical toxicity and the oxidative stress induced by the internal exposure of uranium is responsible for the long-term adverse effect of in vivo contamination of uranium. An agent with simultaneous removal capability of uranium and excess reactive oxygen species (ROS) is highly desired. Herein, the lacunary Keggin-type polyoxometalate (POM) is demonstrated to selectively bind with uranyl ions in the presence of excess essential divalent ions and exhibits a compelling ROS scavenging efficiency of 78.8%. In vivo uranium decorporation assays illustrate the uranium sequestration efficiencies of 74.0%, 49.4%, and 37.1% from kidneys by prophylactic, prompt, and delayed administration of lacunary POM solution, respectively. The superior ROS quenching and uranium removal performance in comparison with all reported bifunctional agents endow lacunary polyoxometalates as novel agents to effectively protect people from injuries caused by the internal exposure of actinides.

CLASSIFICATION OF MEDICAL EQUIPMENT FOR ANTI-RADIATION PROTECTION. / KLASYFIKATsIIa MEDYChNYKh ZASOBIV PROTYRADIATsIINOGO ZAKhYSTU.

Any collection of objects of study needs some arrangement, i. e. classification. The existing numerous classifications of antiradiation agents are built on the basis of their antiradiation effects of an integrated or differentiated nature. The work presents the chronology of the main classifications of chemical compounds that are able to protect against the shortterm and longterm effects of ionizing radiation when they are introduced into the body both before and after exposure. The change of views, trends and paradigms regarding radioprotective compounds is shown. These classifications of antiradiation medicines include radioprotectors, means of stimulating the radioresistance of the body, means of prevention and suppression of the primary reaction to irradiation, means of prevention and treatment of lesions from exposure to incorporated radionuclides, means of treatment of acute bone marrow syndrome, means of treatment of local radiation lesions. It is shown that modern concepts of radiation protection are based on fundamentally different «points of application¼ of groups of radioprotective agents and depend on the stage of radiation damage.

Effect of NBED on decorporation of uranium and protective effect on HK-2 cellular damage / 中国药理学通报

Aim To study the effect of NBED on the decorporation of uranium and the protective effect on HK-2 cellular damage.Methods ICR mice were divided into control group, uranium exposure group(0.03 mg), DTPA-CaNa3(300 mg·kg-1)and NBED(300, 150, 75 mg·kg-1)treatment groups.After injection of uranyl acetate, mice were given different doses of decorporation agents immediately.After 24 h the content of uranium in kidney, bone, liver, spleen and muscle was determined by ICP-MS.HK-2 cells were divided into control group, uranium model group(80 μmol·L-1), DTPA-CaNa3(80 μmol·L-1)and NBED(80, 40, 20 μmol·L-1)treatment group interacted with uranium for 48h.CCK-8 method was used to detect the cell survival rate; light microscope was used to observe the cell morphology; ICP-MS method was used to detect the ratio of uranium endocytosis and uranium efflux; biochemical method was employed to determine SOD, GSH and LDH levels; flow cytometry was applied to determine ROS, apoptosis and cell cycle.Results 300 mg·kg-1 NBED reduced the content of uranium in kidney and bone by 44.3% and 18.8% respectively.Compared with model group, NBED reduced uranium entry into cells by 11%42%, increased uranium emission by 18%48%, increased the survival rate of HK-2 cells, thelevels of SOD and GSH, decreased the expression levels of ROS and LDH, and decreased the apoptotic rate and S phase arrest.DTPA-CaNa3 could significantly reduce the content of uranium and the amount of uranium endocytosis in kidney of mice, but the effect of promoting excretion was significantly lower than that of NBED, and it had no protective effect on the acute injury of HK-2 cells caused by uranium.Conclusions NBED is an effective uranium decorporation agent, which is superior to DTPA-CaNa3 approved by FDA.It could reduce the production of ROS and LDH, increase the content of SOD and GSH, and reduce the arrest and apoptosis of S phase, thus protecting HK-2 cells from uranium induced damage.

Experimental Evaluation of 65Zn Decorporation Kinetics Following Rapid and Delayed Zn-DTPA Interventions in Rats. Biphasic Compartmental and Square-Root Law Mathematical Modeling.

The decorporation kinetics of internal radionuclide contamination is a long-term treatment raising modeling, planning, and managing problems, especially in the case of late intervention when the radiotoxic penetrated the deep compartments. The decorporation effectiveness of the highly radiotoxic 65ZnCl2 by Zn-DTPA (dosed at 3.32 mg and 5 mg/0.25 mL/100 g body weight) was investigated in Wistar male rats over a ten-day period under various treatments (i.e., as a single dose before contamination; as a single dose before and 24 h after contamination; and as daily administrations for five consecutive days starting on day 12 after contamination). The radioactivity was measured using the whole-body counting method. Mono- and bi-compartmental decorporation kinetics models proved applicable in the case of a rapid intervention. It was found that a diffusion model of the radionuclide from tissues to blood better describes the decorporation kinetics after more than ten days post treatment, and the process has been mathematically modeled as a diffusion from an infinite reservoir to a semi-finite medium. The mathematical solution led to a square-root law for describing the 65Zn decorporation. This law predicts a slower release than exponential or multiexponential equations, and could better explain the very long persistence of radionuclides in the living body. Splitting data and modeling in two steps allows a better understanding, description and prediction of the evolution of contamination, a separate approach to the treatment schemes of acute and chronic contamination.

Treatment of radiological contamination: a review.

After nuclear accidents, people can be contaminated internally via ingestion, inhalation and via intact skin or wounds. The assessment of absorbed, committed doses after internal exposure is based on activity measurement byin vivoorin vitrobioassay. Estimation of dose following internal contamination is dependent on understanding the nature and form of the radionuclide. Direct counting methods that directly measureγ-rays coming from within the body or bioassay methods that measure the amount of radioactive materials in urine or feces are used to estimate the intake, which is required for calculating internal exposure doses. The interpretation of these data in terms of intake and the lifetime committed dose requires knowledge or making assumptions about a number of parameters (time, type of exposure, route of the exposure, physical, biological and chemical characteristics) and their biokinetics inside the body. Radioactive materials incorporated into the body emit radiation within the body. Accumulation in some specific organs may occur depending on the types of radioactive materials. Decorporation therapy is that acceleration of the natural rate of elimination of the contaminant will reduce the amount of radioactivity retained in the body. This article presents an overview of treatment of radiological contamination after internal contamination.

Comparison of Local and Systemic DTPA Treatment Efficacy According to Actinide Physicochemical Properties Following Lung or Wound Contamination in the Rat.

Purpose: In cases of occupational accidents in nuclear facilities or subsequent to terrorist activities, the most likely routes of internal contamination with alpha-particle emitting actinides, such as plutonium (Pu) and americium (Am), are by inhalation or following wounding. Following contamination, actinide transfer to the circulation and subsequent deposition in skeleton and liver depends primarily on the physicochemical nature of the compound. The treatment remit following internal contamination is to decrease actinide retention and in consequence potential health risks, both at the contamination site and in systemic retention organs as well as to promote elimination. The only approved drug for decorporation of Pu and Am is the metal chelator diethylenetriaminepentaacetic acid (DTPA). However, a limited efficacy of DTPA has been reported following contamination with insoluble actinides, irrespective of the contamination route. The objectives of this work are to evaluate the efficacy of prompt local and/or systemic DTPA treatment regimens following lung or wound contamination by actinides with differing solubility. The conclusions are drawn from retrospective analysis of experimental studies carried out over 10 years. Materials and Methods: Rat lungs or wounds were contaminated either with poorly soluble Mixed OXide (U, Pu O2) or more soluble forms of Pu (nitrate or citrate). DTPA treatment was administered promptly after contamination, locally to lungs by insufflation of a powder or inhalation of aerosolized solution or by injection directly into the wound site. Intravenous injections of DTPA were given either once or repeated in combination with the local treatment. Doses ranged from 1 to 30 µmol/kg. Animals were euthanized from day 7-21 and alpha activity levels were measured in urine, lungs, wound, bone and liver for determination of decorporation efficacy. Results: Different experiments confirmed that whatever the route of contamination, most of the activity is retained at the entry site after insoluble MOX contamination as compared with contamination with more soluble forms which results in very low activities reaching the systemic compartment and subsequent retention in bone and liver. Several DTPA treatment regimens were evaluated that had no significant effect on either lung or wound levels compared with untreated animals. In contrast, in all cases systemic retention (skeleton and liver) was reduced and urinary excretion were enhanced irrespective of the contamination route or DTPA treatment regimen. Conclusion: The present study demonstrates that despite limitation of retention in systemic organs, different DTPA protocols were ineffective in removing insoluble actinides deposited in lungs or wound site. For moderately soluble actinides, local or intravenous DTPA treatment reduced activity levels both at contamination and at systemic sites.

Characterization of Thorium-Pyrazinoic acid complexation and its decorporation efficacy in human cells and blood.

Thorium (Th) exposure to the human beings is a radiochemical hazard and the chelation therapy by suitable drugs is the major prevention approach to deal with. The present studies aimed at usage of pyrazinoic acid (PCA), which is a prodrug to treat tuberculosis, for its usage as decorporating agent for thorium from human body. The present studies provide a comprehensive knowledge on the chemical interaction and biological efficacy of pyrazinoic acid (PCA) for decorporation of Thorium from the human body. The thermodynamic parameters for Th-PCA speciation are determined by both experiment and theory. The potentiometric data analysis and Electro-Spray Ionization Mass Spectrometry (ESI-MS) studies revealed the formation of MLi (i = 1-4) species with the decrease in stepwise stability constants. All the species formations are endothermic reactions and are predominantly entropy-driven. Biological experiments using human erythrocytes, whole blood and normal human lung cells showed cytocompatibility and decorporation ability of PCA for Thorium. Density functional calculations have been carried out to get insights on interaction process at molecular level. The experimental results and theoretical predictions found to be in line with each other. Present findings on complexation of Th by PCA and its evaluation in human cells and blood would further motivate determination of its safety levels and decorporation efficacy in animal models.

Preparing for a "dirty bomb" attack: the optimum mix of medical countermeasure resources.

BACKGROUND: In radiological emergencies with radionuclide incorporation, decorporation treatment is particularly effective if started early. Treating all people potentially contaminated ("urgent treatment") may require large antidote stockpiles. An efficacious way to reduce antidote requirements is by using radioactivity screening equipment. We analyzed the suitability of such equipment for triage purposes and determined the most efficient mix of screening units and antidote daily doses. METHODS: The committed effective doses corresponding to activities within the detection limits of monitoring portals and mobile whole-body counters were used to assess their usefulness as triage tools. To determine the optimal resource mix, we departed from a large-scale scenario (60,000 victims) and based on purchase prices of antidotes and screening equipment in Germany, we calculated efficiencies of different combinations of medical countermeasure resources by data envelopment analysis. Cost-effectiveness was expressed as the costs per life year saved and compared to risk reduction opportunities in other sectors of society as well as the values of a statistical life. RESULTS: Monitoring portals are adequate instruments for a sensitive triage after cesium-137 exposure with a high screening throughput. For the detection of americium-241 whole-body counters with a lower daily screening capacity per unit are needed. Assuming that 1% of the potentially contaminated patients actually need decorporation treatment, an efficient resource mix includes 6 monitoring portals and 25 mobile whole-body counters. The optimum mix depends on price discounts and in particular the fraction of victims actually needing treatment. The cost-effectiveness of preparedness for a "dirty bomb" attack is less than for common health care, but costs for a life year saved are less than for many risk-reduction interventions in the environmental sector. CONCLUSION: To achieve economic efficiency a high daily screening capacity is of major importance to substantially decrease the required amount of antidote doses. Among the determinants of the number of equipment units needed, the fraction of the potentially contaminated victims that actually needs treatment is the most difficult to assess. Judging cost-effectiveness of the preparedness for "dirty bomb" attacks is an issue of principle that must be dealt with by political leaders.

pH-dependent Release Matrix Oral Formulation of Prussian Blue to Improve its Efficacy as an Internal Decorporation Agent.

BACKGROUND: Prussian Blue (PB) is available as conventional release dosage form "Radiogardase" with effective daily dose of 3-10 g (very high). The target site is the duodenum, where it inhibits the enterohepatic circulation of Cs & Tl ions, enhancing their fecal excretion. OBJECTIVE: To enhance efficacy, target release, reduce the dose and side effects, oral pH-dependent matrix formulation of PB based on in-situ gelation of sodium alginate along with calcium salts was formulated and evaluated. METHODS: Different combinations of matrix granules were formulated and optimized. The optimized one was compressed using Polyvinylpyrrolidone K30 (Pvp K30) in different batches and optimized. Langmuir adsorption isotherm was used to assess in-vitro binding efficacy of formulation to thallium using atomic absorption spectroscopy. The proof of concept i.e., drug release in the duodenum was studied through pharmacoscintigraphy using radiolabeled formulation in rabbits. RESULTS: The optimized granules showed no drug release in an acidic medium for 2 h whereas complete empty of the basket in a basic medium within 30-60 minutes. The matrix tablet formulation with Pvp K30 (10% w/w) was optimized with desired hardness and optimum in-vitro release profile. The release data fitted to various linear kinetic models, Hixson-Crowell r2 (0.9906) best fit, confirmed the erosion-based release mechanism. The maximum binding capacity (MBC) was found significantly higher (89.60 mg Tl/g formulation) than that of PB API (65.90 mg Tl /g PB API). Pharmacoscintigraphic images confirmed intact formulation in the stomach up to 2h and burst release in intestine thereafter. CONCLUSION: The results exemplify oral pH-dependent PB matrix formulation which achieved desirable target release at the duodenum and in-vitro binding efficacy towards Tl ion was appreciable.

Application of nanoformulations and nanomaterials in the decorporation of radionuclides / 中华放射医学与防护杂志

Internal contamination of radionuclides in the event of nuclear emergencies can lead to serious harm to human health. The research and development of radionuclide chelating agents and the application of new technologies can reduce the internal damage caused by radionuclides. Compared with traditional preparations, the nano-preparations have the advantages of improving drug dissolution, targeting and positioning drug release, and easily passing through biofilm barrier. In recent years, many scholars have used different nano-preparation forms for different decorporation drugs, including nanoparticles, nano-liposomes, nano-emulsions, etc., to conduct related research in order to achieve better clinical application effects. Nanomaterials with excellent properties have the advantages of high efficiency, rapid adsorption and high biocompatibility, etc., and have been used more and more widely in radionuclide decorporation. In this paper, combined with the relevant literatures at home and abroad, the internal contamination of radionuclides is classified according to nuclide-deposited sites of tissues and organs, and the applications of related nanoformulations and nanomaterials in radionuclide decorporation are introduced in order to provide reference for further research.