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Nanoparticles has many properties, especially in treatment of medical field, but the controversy continues about their cytotoxicity. Hence, this research was conducted to estimate the concentration of gold nanoparticles (GNPs) in tumor and other organs such as kidney, liver, and spleen after injection GNPs by two routes, intratumor and intraperitoneal to compare between two methods in mice implanted with mammary adenocarcinoma for 28 days. Atomic Absorption Spectroscopy was used to measure the GNPs concentrations. The results revealed that the GNPs concentrations were significantly (P≤0.05) increased (3.75±1.75, 2.42 ±0.31 ppm) in kidney tissue after intratumor and intraperitoneal administration, respectively, when compared to the other organs (liver and spleen), followed by tumor mass (2.66±0.01, 1.09 ±0.06 ppm) in tissue. While the concentrations of GNPs in spleen and liver were (1.40 ±0.33, 0.726 ±0.01) and (0.602 ±0.03, 0.517 ±0.02) after intratumor and intraperitoneal administration respectively. Also, the experiment showed that the injection by intratumor was more efficient than intraperitonial method for tumor treatment, so, the nanoparticles were cleared by responsible lymphoid organs of body.

Background:68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases.Methods:We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented.Results:Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis.Discussion:Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice.Conclusion:The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

This study aims to review, analyze and systematize the knowledge created on bio-economy to develop a conceptual and theoretical framework based on the transdisciplinary study of biology and socioeconomy to be used in further research. It begins from the questioning of what are the benefits that bio-economy has compared to the neoclassical economy. The methods employed are the critical analytic, descriptive, deductive-inductive and suggests a holistic and transdisciplinary approaches. As a result, the core of the study presents the principles under which this new scientific paradigm in sustainable development can continue creating more scientific knowledge to be used in the formulation and implementation of strategic choices for the bio production, bio distribution and bio consumption process. Este estudio tiene como objetivo revisar, analizar y sistematizar el conocimiento creado sobre la bioeconomía para desarrollar un marco conceptual y teórico basado en el estudio transdisciplinario de la biología y la socioeconomía para ser utilizado en futuras investigaciones. Comienza desde el cuestionamiento de cuáles son los beneficios que la bioeconomía tiene en comparación con la economía neoclásica. Los métodos empleados son analíticos críticos, descriptivos, deductivos-inductivos y sugieren enfoques holísticos y transdisciplinarios. Como resultado, el núcleo del estudio presenta los principios bajo los cuales este nuevo paradigma científico en el desarrollo sostenible puede continuar creando más conocimiento científico para ser utilizado en la formulación e implementación de elecciones estratégicas para el proceso de bioproducción, biodistribución y bioconsumo. Este estudo tem como objetivo revisar, analisar e sistematizar o conhecimento criado sobre bioeconomia para desenvolver um arcabouço conceitual e teórico baseado no estudo transdisciplinar da biologia e da socioeconomia a ser utilizado em futuras pesquisas. Começa com o questionamento de quais são os benefícios que a bioeconomia possui comparada à economia neoclássica. Os métodos empregados foram o analítico crítico, descritivo, dedutivo-indutivo e sugere uma abordagem holística e transdisciplinar. Como resultado, o cerne do estudo apresenta os princípios sob os quais este novo paradigma científico em desenvolvimento sustentável pode continuar criando mais conhecimento científico a ser usado na formulação e implementação de escolhas estratégicas para o processo de bio-produção, bio-distribuição e bio-consumo.

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO2, ZnO and Ag NPs, are among the most popular NPs found in commercially available products. They may also have potential applications in biomedicine, which could increase their contact with cardiovascular systems. This review aimed at providing an overview about the adverse cardiovascular effects of TiO2, ZnO and Ag NPs. We discussed about the bio-distribution of NPs following different exposure routes. We also discussed about the cardiovascular toxicity of TiO2, ZnO and Ag NPs as assessed by in vivo and in vitro models. The possible mechanisms and contribution of physicochemical properties of metal based NPs were also discussed.

Along with the increasing applications of nanomaterials in medical fields, to know the systemic distribution of nanomaterials in the body through a precise method is required for the biosafety assessment of nanomaterials. In this study, we firstly have established a reliable inductively coupled plasma mass spectrometry (ICP-MS) method for concentration measurement of silver (Ag) and gold (Au) in biological tissues. Then, based on this method, the Ag or Au distribution in rat blood and almost all of the organs were analyzed after an i.v. or s.c. administration of Au@Ag NRs. Both the time-dependent contents of Ag and Au in blood and two pharmacokinetic models confirmed the rapid clearance of Ag from blood. At 24 h after i.v. injection, there was the highest level of Ag in liver, followed by portal nodes, spleen, lung, bone marrow and pancreas. In addition, we also found there were gender-related distributions of Ag and Au in some organs, especially after s.c. injection. Therefore, these more comprehensive and important results would give fundamental information for the biological risk assessment of nanomaterials.

During the last three decades, dendrimers, nano-sized highly-branched fractal-like symmetrical macromolecules, have been intensively studied as promising candidates for application as drug-delivery carriers. Among other important characteristics arising from their unique and highly-controlled architecture, size and surface properties, the possibility of hosting guest molecules in internal voids represents a key advantage underlying the potential of dendrimers as non-covalent drug-encapsulating agents. The impressive amount of accumulating experimental results to date allows researchers to identify the most important and promising theoretical and practical aspects of the use of dendrimers for this purpose. This review covers the main factors, phenomena, and mechanisms involved in this drug-vectorization approach, including mechanisms of non-covalent dendrimer-drug association, dendrimer-dendrimer interactions, as well as biological properties relevant to the host dendrimers. A discussion is then provided to illustrate some successful existing formulation strategies as well as to propose some new possible ones to optimize further development of the field.

Measurement of uptake by using the image based bio-distribution of 99mTc-DMSA (Dimercapto succinic acid) and 99mTc-DTPA (Diethylene triaminepenta acetic acid) in Kidney, Spleen and Liver with frame to frame analysis has been evidenced as the simplified way than the existing computer program based methodology, like MIRD and others. In this study, 100 patients were included in each scan. For 99mTc-DTPA scan, the mean uptake percentage for Kidney was 84.06% and that for Spleen was 7.80% and for Liver was 8.13% in which 66 patients were male and 34 were female age ranging from 3 (three) months to 70 (seventy) years. On the other hand,99mTc-DMSA scan was executed for 60 (sixty) male and 40 (forty) female patients; the mean values of uptake percentage for Kidney, Spleen and Liver were 87.40%, 5.99% and6.60% respectively. It was manifested that the uptake percentages of radiopharmaceuticals were the highest in kidney for youngers whereas those values in other organs were lower than adults.Journal of Bangladesh Academy of Sciences, Vol. 41, No. 1, 105-114, 2017

Introduction The 11 C/ 18 F–choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F–choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F–choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F–choline bio-distribution in the female body. Methods We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F–choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F–choline PET/CT in 5 female patients. Results 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. Conclusions The accurate knowledge of 18 F–choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F–choline uptake in the exocrine glands. Advances in knowledge Our results confirm the possibility of 18 F–choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F–choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. Implications for patient care The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a better patient quality of life.

We couple a tumor growth model embedded in a microenvironment, with a bio distribution model able to simulate a whole organ. The growth model yields the evolution of tumor cell population, of the differential pressure between cell populations, of porosity of ECM, of consumption of nutrients due to tumor growth, of angiogenesis, and related growth factors as function of the locally available nutrient. The bio distribution model on the other hand operates on a frozen geometry but yields a much refined distribution of nutrient and other molecules. The combination of both models will enable simulating the growth of a tumor in a whole organ, including a realistic distribution of therapeutic agents and allow hence to evaluate the efficacy of these agents.

Quantum dots (QDs) comprise an emerging group of materials with innumerable number of possibilities in biological research including cellular labelling. Among the leading members in this category, ZnSe/ZnS quantum dots (QDs) hold greater attractive possibilities in imaging primarily due to their higher biocompatibility and dispersibility. Nevertheless, the inherent toxicity of ZnSe/ZnS QDs is not yet completely explored which largely compromise most of their biomedical application potential. Strong blue emitting water soluble QDs effectively synthesized by aqueous phase route. Synthesized QDs further subjected to various optical and physicochemical characterization. Approximately 5–6 nm sized ZnSe/ZnS QDs illuminated bluish green fluorescence under UV lamp. Present study addresses possible adverse effects of ZnSe/ZnS QDs in hepatic system using HepG2 cells; which is the routinely employed in vitroliver cell model. A bundle of assays wasperformed out to reveal the cytotoxic nature of ZnSe/ZnS QDs and the mechanism behind it. Herein, absorption, distribution, metabolism, excretion and toxicity (ADME and T) of ZnSe/ZnS in mice were profiled in detail followed by intravenous (i.v.) and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight. In a short review, it could be state that ZnSe/ZnS QDs did not exhibit any significant in vivo toxicity outcome in mice.

Metformin, an anti-diabetes drug, has been recently emerging as a potential “anti-aging” intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.

A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ∼5 nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10 nM, for 6 and 24 h. Accumulation of dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on trophoblast integrity and endocrine function, LDH, and hCG releases were measured. A dose- and charge-dependent accumulation of dPG-NPs was observed at the early placental barrier and in cell lines, with positive dPG-NP-surface causing deposits even in the mesenchymal core of the placental villi. No signs of plasma membrane damage could be detected. After 24 h we observed a significant reduction of hCG secretion in placental explants, without significant changes in trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NP’s surface charge substantially influences their bio-distribution at the feto-maternal interface, with positive charge facilitating trans-trophoblast passage, and in contrast to more artificial models, the first-trimester placental explant culture model reveals potentially hazardous influences of charged dPG-NPs on early placental physiology.

Aim: The present research work was aimed at developing a self-microemulsifying drug delivery system (SMEDDS) of Primaquine (PQ) with increased liver uptake and hence enhanced antimalarial efficacy against the liver stages of Plasmodium vivax. Materials and methods: SMEDDS was formulated using generally regarded as safe (GRAS) excipients and adsorbed on Aerosil 200. The optimized SMEDDS were characterized for various physicochemical parameters. Pharmacodynamic efficacy in murine model was evaluated using Peter’s Four Day Suppresive Test. Biodistribution studies were carried out using flow cytometry. Results: The adsorbed SMEDDS showed a particle size of 75 nm and exhibited enhanced antimalarial efficacy as compared to marketed formulations. Biodistribution studies revealed enhanced uptake in the liver. Conclusion: Preliminary studies in lower animals indicated the potential of SMEDDS to enhance the uptake of PQ at its site of action i.e. liver.

RESUMO Ricinus communisé uma planta pertence à família Euforbiaceae. A partir de seus frutos é extraído o óleo de rícino e outra fração altamente tóxica (fração não-oleosa). Neste estudo, foi avaliado o efeito da fração não oleosa de R. communis(FNORC) na biodistribuição do Tc-99m em camundongos sadios e em animais transplantados com Sarcoma-180 (S180). Para avaliação da biodistribuição do Tc-99m, o percentual de atividade radioativa total injetada (ATI%) foi mensurada utilizando um contador gama. Os resultados mostraram que, em animais sadios, houve aumento da captação do Tc-99m após o tratamento com FNORC pelos rins, cérebro e estômago. Apenas houve diminuição da absorção deste radioisótopo nos músculos. Em animais com tumor, houve redução significativa da captação do Tc-99m no coração, pulmões e tumor, e foi observado o aumento da captação apenas nos rins. Foi observada também a diminuição da concentração das proteínas plasmáticas totais em animais com tumor após tratamento com FNORC e atividade antitumoral significativa. Diante desses dados, conclui-se que fração não oleosa de R. communis possui atividade antitumoral significativa, porém altera a biodistribuição do Tc-99m, fato este que pode resultar em falhas nos processos de diagnóstico por imagem que utilizem este radioisótopo como marcador. ABSTRACT Ricinus communis is a plant belonging to the Euforbiaceae family. From its fruits, it is extracted the castor oil and another highly toxic fraction (non-oily fraction). In this study, we evaluated the effect of the non-oily fraction of R. communis (NOFRC) on the bio distribution of Tc-99m in healthy mice and in animals transplanted with Sarcoma-180 (S180). To evaluate the bio distribution of theTc-99m, the percentage of the total injected radioactivity (% TIR) was measured through a gamma counter. There was an increase in the capitation of Tc-99m after the treatment with NOFRC in the kidneys, brain, and stomach of healthy animals. A decrease in the reception of this radionuclide was only found in the muscles. In animals with tumour, there was a significant reduction in the uptake of Tc-99m in the heart, lungs and tumour. An increase in the capitation was only observed in the kidneys. It was also observed a reduction in the total plasma protein concentration in animals with tumours after the treatment with NOFRC, besides significant antitumor activity. We concluded that there is antitumor activity in the NOFRC, but that it alters the biodistribution of Tc-99m, a fact which may result in failures in the diagnostic imaging process using this radioisotope as a marker.

Currently there is a lack of in vivo techniques to evaluate the spatial bio-distribution of dermal drugs over time without the need to take multiple serial biopsies. To address this gap, we investigated the use of multi-photon optical imaging methods to non-invasively track drug distribution on miniature pig (Species: Sus scrofa, Strain: Gottingen) skin in vivo. Minipig skin is the standard comparative research model to human skin, and is anatomically and functionally similar. We employed fluorescence lifetime imaging microscopy (FLIM) to visualize the spatial distribution and residency time of a topically applied experimental dermatological cream. This was made possible by the endogenous fluorescent optical properties of the experimental drug (fluorescence lifetime > 3000 ps). Two different drug formulations were applied on 2 minipigs for 7 consecutive days, with the control creams applied on the contralateral side, followed by 7 days of post-application monitoring using a multi-modal optical imaging system (MPTflex-CARS, JenLab, Germany). FLIM images were obtained from the treated regions 24 hr post-application from day 1 to day 14 that allowed visualization of cellular and sub-cellular features associated with different dermal layers non-invasively to a depth of 200 µm. Five punch biopsies per animal were obtained from the corresponding treated regions between days 8 and 14 for bioanalytical analysis and comparison with results obtained using FLIM. In conclusion, utilization of non-invasive optical biopsy methods for dermal drug evaluation can provide true longitudinal monitoring of drug spatial distribution, remove sampling limitations, and be more time-efficient compared to traditional methods.

Objective:Therapeutic effects of thyme and the mechanism underlying the function of its active ingredients are the areas of active investigation. In this regard, understanding the potential interactions between the active ingredients of the thyme leaf and the serum albumin would bring about new insight on the bio-distribution, circulatory half-life and consequently their pharmacodynamics and pharmacokinetic properties.Methods:The 3D structures of carvacrol, linalool, p-cymene and thymol molecules as the thyme active ingredients and the 3D structure of albumin were harnessed from the structural databases. Then, these structures were prepared for molecular docking analyses by Autodock vina software. Ultimately, the binding energies between docked albumin and thyme active ingredients were calculated and their interactions were predicted.Results:Our results indicated that all active ingredients of thyme can interact with albumin molecule at drug binding site 3 and fatty acid binding site 5. The structural properties of the ingredients effect their interaction sites and binding energies.Conclusion:It could be concluded that albumin, as the most abundant protein of the serum, could act as the bio-distributor of thyme active ingredients. This property would be of great significance to exert the desired therapeutic effects.

A new contrast agent in medical imaging discovered and developed since 10 years ago and it’s under study until this moment because the classic contrast agents impose earnest limitations on medical imaging abilities such as the short imaging time, poor contrast X-ray images for obese patients (over weighted patients) and real side effects renal problems and toxicity problems. The new contrast agent is the Gold Nanoparticles (GNP) may overcome these restrictions due to its properties where the (GNP) bio distribution is higher than tri-iodobenzene compounds. also, bone /tissue interference is more clear and obvious than tri-iodobenzene compounds and in general nanoparticles clear the blood slowly than classic contrast agents which permit for longer imaging time and all of that leads to enhancing the X-ray diagnostic. Gold Nanoparticles were injected intraperitoneally into mice then images were taken by conventional X-RAY unit. Tumors were seen clearly.

The present study was designed to understand the influence of zinc (Zn) if any, on the biokinetics of (65)Zn in brain as well as whole body and its bio-distribution following aluminium (Al) treatment to rats. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups viz: normal control, aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/L in drinking water) and combined aluminium and zinc treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment showed a significant increase in fast component (Tb1) but revealed a significant decrease in slow component (Tb2) of biological half-life in brain as well as in whole body. However, Zn supplementation to Al-treated rats reversed the trend in both brain and whole body, which indicates a significant decrease in Tb1 component while the Tb2 component was significantly increased. Further, Al treatment showed an increased percent uptake value of (65)Zn in cerebrum, cerebellum, heart, liver and lungs whereas a decrease in uptake was found only in blood. On the other hand, there was a significant decline in (65)Zn activity in nuclear and mitochondrial fractions of brain of Al-treated rats. However, Zn treatment reversed the altered (65)Zn uptake values in different organs as well as in various subcellular fractions. The study demonstrates that Zn shall prove to be effective in regulating the biokinetics of (65)Zn in brain and whole body and its distribution at the tissue and subcellular levels in Al-treated rats.

Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

In this study, 99mTc- phthalic acid (PA) firstly, was prepared with a high radiochemical yield up to 98% that confirmed with different chromatographic techniques by using 2 mg phthalic acid, 50 μg SnCl2·2H2O as a reducing agent, in solution of pH 7 at room temperature for 30 min. Secondly, 99mTc-tricarbonyl phthalic acid was prepared under 30 min heating at 100°C. Bio distribution studies were carried out in Albino Swiss mice in which 99mTc-PA and 99mTc-tricarbonyl PA were concentrated in kidneys and intestine. This work aims to evaluation of labeled PA as a model for Potential Hazards imaging in vitro and in vivo toxicity in Albino Swiss mice.

This paper gives a general overview about bio distribution studies which are especially related to engineered nanoparticles (NPs) made of gold and silver. The analysis of biological materials from bio distribution studies plays a significant role in the application of atomic spectrometry to study NPs. Therefore, special focus is given to the generally applied strategy as well as the use of the inductively coupled plasma mass spectrometry (ICP-MS) technique for the determination of the NPs containing metals. An overview of the recent research applications on gold and silver NPs is also presented. While for gold NPs a large variety of very different sizes, shape and coating are known, they also provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their bio kinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment. Silver NPs are applied in a lot of consumer products; therefore it is useful to get a better understanding of their in vivo distribution. © 2012 Elsevier B.V.

Background: Recent clinical studies suggest that the prophylactic use of recombinant factor VIIa (rFVIIa) markedly reduces the number of bleeding episodes in hemophilic patients with inhibitors. Given the short biological half-life of rFVIIa, it is unclear how rFVIIa could be effective in prophylactic treatment. Objectives: To examine the extravascular distribution of pharmacologically administered rFVIIa to obtain clues on how rFVIIa could work in prophylaxis. Methods: Recombinant mouse FVIIa tagged with AF488 fluorophore (AF488-FVIIa) was administered into mice via the tail vein. At different time intervals following the administration, mice were exsanguinated and various tissues were collected. The tissue sections were processed for immunohistochemistry to evaluate distribution of rFVIIa. Results: rFVIIa, immediately following the administration, associated with the endothelium lining of large blood vessels. Within 1 h, rFVIIa bound to endothelial cells was transferred to the perivascular tissue surrounding the blood vessels and thereafter diffused throughout the tissue. In the liver, rFVIIa was localized to sinusoidal capillaries and accumulated in hepatocytes. In bone, rFVIIa was accumulated in the zone of calcified cartilage and some of it was retained there for a week. The common finding of the present study is that rFVIIa in extravascular spaces was mostly localized to regions that contain TF expressing cells. Conclusions: The present study demonstrates that pharmacologically administered rFVIIa readily associates with the vascular endothelium and subsequently enters into extravascular spaces where it is likely to bind to TF and is retained for extended time periods. This may explain the prolonged pharmacological effect of rFVIIa. (Less)

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

INTRODUCTION: Endothelial progenitor cells (EPCs) has been reported to have the potential for advancing revascularization of ischemic tissue. However, the heterogeneous nature of these cells calls for specification of the angiogenic potential of each subtype. The purpose of this study was to gain additional insight on the homing capacity of the EPC subtype, endothelial outgrowth cells (EOCs) in tumours using a well-established tumour model.METHODS: (111)Indium ((111)In) - and 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelled EOCs derived from human umbilical cord blood were injected into mice with a C3H mammary carcinoma foot tumour. The subsequent capture of the EOCs was traced by estimation of activity in individual organs, autoradiography and fluorescence microscopy.RESULTS: (111)In activity was found in tumour and other organs. However, varying parts of the activity originated from free (111)In lost from EOCs. Autoradiography demonstrated accumulation of (111)In activity in the tumour rim. Microscopy proved that a least part of this radioactivity originated from the presence of human derived EOCs and that those EOCs were not located in the endothelial lining of vessels, in the tumour.CONCLUSION: The results demonstrated the presence of xenotransplanted EOCs in the rim of a C3H mammary carcinoma. They were, however, not located in the endothelial lining of the vessels, thus indicating that their effect in vasculogenesis might be mediated via paracrine mechanisms rather than differentiating into endothelial cells (ECs) in tumour vessels.

Manufactured nanomaterials have been shown to be beneficial in an array of applications, including diagnosis and targeted abolition of tumour cells. The biocompatibility and bio-distribution of the...

PDT agent exhibited heterogeneity over a tumor area. Our non-invasive, fluorescence tomography system reconstructed the agent bio-distribution in 3D. Accurate localization was performed with, non-concurrent, high frequency Ultrasound imaging system.

Nobiliside A (Nob) is a new triterpenoid saponin separated from Holothuria noblilis. In this article, a liquid chromatography-electrospray ionization-tandem mass spectrometry method was established to quantify Nob, a hemolytic saponin, in rat blood and tissue homogenates. Standard curves were linear (r=0.9988-0.9995) over the range 50-5000ng/mL in blood and 100-10000ng/g in tissues. The lower limit of quantification (LLOQ) was 50ng/mL for Nob. The novel method was rapid, accurate, highly sensitive and highly selective. Using this method, the pharmacokinetics and biodistribution of Nob liposome and Nob solution in Sprague-Dawley rats after a single intravenous dose of 1mg/kg were then investigated. Nob was cleared slowly from circulation. There was no significant difference of the pharmacokinetic parameters in blood between Nob solution and Nob liposome. The highest AUC of Nob was observed in liver for the two groups, followed by spleen, lungs, kidney and heart. Compared with Nob solution, Nob liposome showed much higher AUC in liver and spleen and much lower AUC in kidney, heart and lung, which might be one important reason for the decreased toxicity of Nob.

We report the development of a novel multispectral imaging system that is capable of creating ?m-resolution three dimensional color and fluorescence volumes of optical agents bio-distribution in small animals and organs using epi-illumination fluorescence imaging.