Displaying publications 1 - 20 of 86 in total

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  1. Investigation of a broad diversity of nanoparticles, including their processes, as well as toxicity testing in diverse organs and systems
    Khan AU, Qutob M, Gacem A, Rafatullah M, Yadav KK, Kumar P, et al.
    Toxicology, 2024 Dec;509:153985.
    PMID: 39510373 DOI: 10.1016/j.tox.2024.153985
    Nanotechnology arising in wide-ranging areas, covers extensively different ranges of approaches attained from fields such as biology, chemistry, physics, and medicine engineering. Nanoparticles are a necessary part of nanotechnology effectually applied in the cure of a number of diseases. Nanoparticles have gained significant importance due to their unique properties, which differ from their bulk counterparts. These distinct properties of nanoparticles are primarily influenced by their morphology, size, and size distribution. At the nanoscale, nanoparticles exhibit behaviours that can enhance therapeutic efficacy and reduce drug toxicity. Their small size and large surface area make them promising candidates for applications such as targeted drug delivery, where they can improve treatment outcomes while minimizing adverse effects. The harmful effects of nanoparticles on the environment were critically investigated to obtain appropriate results and reduce the risk by incorporating the materials. Nanoparticles tend to penetrate the human body, clear the biological barriers to reach sensitive organs and are easily incorporated into human tissue, as well as dispersing to the hepatic tissues, heart tissues, encephalum, and GI tract. This study aims to examine a wide variety of nanoparticles, focusing on their manufacturing methods, functional characteristics, and interactions within biological systems. Particular attention will be directed towards assessing the toxicity of nanoparticles in different organs and physiological systems, yielding a thorough comprehension of their potential health hazards and the processes that drive nanoparticle-induced toxicity. This analysis will also emphasize recent developments in nanoparticle applications and safety assessment methodologies.
    Matched MeSH terms: Tissue Distribution
  2. Polymeric Nanoparticles for Brain Drug Delivery - A Review
    Raman S, Mahmood S, Hilles AR, Javed MN, Azmana M, Al-Japairai KAS
    Curr Drug Metab, 2020;21(9):649-660.
    PMID: 32384025 DOI: 10.2174/1389200221666200508074348
    BACKGROUND: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery.

    METHODS: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs.

    RESULTS: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain.

    CONCLUSION: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

    Matched MeSH terms: Tissue Distribution
  3. Fulltext Future Prospective of Radiopharmaceuticals from Natural Compounds Using Iodine Radioisotopes as Theranostic Agents
    Nurhidayah W, Setyawati LU, Daruwati I, Gazzali AM, Subroto T, Muchtaridi M
    Molecules, 2022 Nov 18;27(22).
    PMID: 36432107 DOI: 10.3390/molecules27228009
    Natural compounds provide precursors with various pharmacological activities and play an important role in discovering new chemical entities, including radiopharmaceuticals. In the development of new radiopharmaceuticals, iodine radioisotopes are widely used and interact with complex compounds including natural products. However, the development of radiopharmaceuticals from natural compounds with iodine radioisotopes has not been widely explored. This review summarizes the development of radiopharmaceuticals from natural compounds using iodine radioisotopes in the last 10 years, as well as discusses the challenges and strategies to improve future discovery of radiopharmaceuticals from natural resources. Literature research was conducted via PubMed, from which 32 research articles related to the development of natural compounds labeled with iodine radioisotopes were reported. From the literature, the challenges in developing radiopharmaceuticals from natural compounds were the purity and biodistribution. Despite the challenges, the development of radiopharmaceuticals from natural compounds is a golden opportunity for nuclear medicine advancement.
    Matched MeSH terms: Tissue Distribution
  4. Illuminating Insights: Clinical Study Harnessing Pharmacoscintigraphy for Permeation Study of Radiolabeled Nimesulide Topical Formulation in Healthy Human Volunteers
    Sharma N, Khanna K, Kumar N, Karwasra R, Janakiraman AK, Rajagopal MS
    Assay Drug Dev Technol, 2023 Oct;21(7):325-330.
    PMID: 37801663 DOI: 10.1089/adt.2023.053
    An alternative to oral administration for the delivery of therapeutic substances is the topical route, which frequently has comparable efficacy but may have a better tolerability profile. Gamma scintigraphy is a noninvasive technique that involves the application of radioactive substances to conduct biodistribution studies of therapeutic substances delivered through various routes. Nimesulide (NSD) was radiolabeled with technetium pertechnetate (Technetium99m [99mTc]) and this radiolabeled drug complex (99mTc-NSD) was used to prepare a topical gel formulation. The permeation of the radiolabeled drug from the topical gel was determined by gamma scintigraphy on human volunteers. The region of interest was calculated for the quantification of permeated radiolabeled drugs. This was observed that the mean percentage permeation of 99mTc-NSD was found to be 0.32 ± 0.22 to 36.37 ± 2.86 at 5 and 240 min. It was demonstrated that gamma scintigraphy may be a noninvasive and reliable technique for the determination of drug permeation through topical routes.
    Matched MeSH terms: Tissue Distribution
  5. Prospects and challenges of synergistic effect of fluorescent carbon dots, liposomes and nanoliposomes for theragnostic applications
    Faghihi H, Mozafari MR, Bumrungpert A, Parsaei H, Taheri SV, Mardani P, et al.
    Photodiagnosis Photodyn Ther, 2023 Jun;42:103614.
    PMID: 37201772 DOI: 10.1016/j.pdpdt.2023.103614
    The future of molecular-level therapy, efficient medical diagnosis, and drug delivery relies on the effective theragnostic function which can be achieved by the synergistic effect of fluorescent carbon dots (FCDs) liposomes (L) and nanoliposomes. FCDs act as the excipient navigation agent while liposomes play the role of the problem-solving agent, thus the term "theragnostic" would describe the effect of LFCDs properly. Liposomes and FCDs share some excellent at-tributes such as being nontoxic and biodegradable and they can represent a potent delivery system for pharmaceutical compounds. They enhance the therapeutic efficacy of drugs via stabilizing the encapsulated material by circumventing barriers to cellular and tissue uptake. These agents facilitate long-term drug biodistribution to the intended locations of action while eliminating systemic side effects. This manuscript reviews recent progress with liposomes, nanoliposomes (collectively known as lipid vesicles) and fluorescent carbon dots, by exploring their key characteristics, applications, characterization, performance, and challenges. An extensive and intensive understanding of the synergistic interaction between liposomes and FCDs sets out a new research pathway to an efficient and theragnostic / theranostic drug delivery and targeting diseases such as cancer.
    Matched MeSH terms: Tissue Distribution
  6. Effect of nano-delivery systems on the bioavailability and tissue biodistribution of vitamin E tocotrienols
    Fu JY, Meganathan P, Gunasegaran N, Tan DMY
    Food Res Int, 2023 Sep;171:113048.
    PMID: 37330852 DOI: 10.1016/j.foodres.2023.113048
    Vitamin E is one of the most important essential vitamins to support the regulation of oxidative stress in human body. Tocotrienols are part of the vitamin E family. The potentials of tocotrienols as nutraceutical ingredient are largely understated due to low oral bioavailability, which is a common problem associated with fat-soluble bioactive compounds. Nanoencapsulation technology offers innovative solutions to enhance the delivery mechanisms of these compounds. In this study, the effect of nanoencapsulation on the oral bioavailability and tissue distribution of tocotrienols were investigated using two types of formulations, i.e. nanovesicles (NV-T3) and solid lipid nanoparticles (NP-T3). At least 5-fold increment in maximum plasma concentrations, evident with dual-peak pharmacokinetic profiles, were observed after oral administration of nano-encapsulated tocotrienols. Plasma tocotrienol composition showed a shift from α-tocotrienol dominant in control group (Control-T3) to γ-tocotrienol dominant after nanoencapsulation. Tissue distribution of tocotrienols was found to be strongly influenced by the type of nanoformulation. Both nanovesicles (NV-T3) and nanoparticles (NP-T3) showed elevated accumulation in the kidneys and liver (5-fold) compared to control group while selectivity for α-tocotrienol was evident for NP-T3. In brain and liver of rats given NP-T3, α-tocotrienol emerged as the dominant congener (>80%). Acute oral administration of nanoencapsulated tocotrienols did not show signs of toxicity. The study concluded enhanced bioavailability and selective tissue accumulation of tocotrienol congeners when delivered via nanoencapsulation.
    Matched MeSH terms: Tissue Distribution
  7. Fulltext The pattern of amyloid deposition in the lung
    Looi LM
    Malays J Pathol, 1999 Jun;21(1):29-35.
    PMID: 10879276
    A review of routine histopathological samples and autopsies examined at the Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of the lung. Two were localized depositions limited to the lung while in the remainder, lung involvement was part of the picture of systemic amyloidosis. Both cases of localized amyloidosis presented with symptomatic lung/bronchial masses and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated with heavy plasma cell and lymphocytic infiltration and the presence of multinucleated giant cells. In both cases, the amyloid deposits were immunopositive for lambda light chains and negative for kappa chains and AA protein. One was a known systemic lupus erythematosus patient with polyclonal hypergammaglobulinaemia. The other patient was found to have plasma cell dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis was not obvious clinically or macroscopically but was histologically evident in 75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of arterioles and small vessels, and along the alveolar septa. It was less frequently detected in the pleura, along the basement membrane of the bronchial epithelium and around bronchial glands. In one case of systemic AL amyloidosis associated with multiple myeloma, an "amyloidoma" occurred in the subpleural region reminiscent of localized amyloidosis. These cases pose questions on (1) whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL amyloidosis and (2) the differing pattern of tissue deposition of different chemical types of amyloid fibrils, with the suggestion that light chain amyloid has a greater tendency to nodular deposition than AA amyloid.
    Matched MeSH terms: Tissue Distribution
  8. Methotrexate-based ionic liquid as a potent anticancer drug for oral delivery: In vivo pharmacokinetics, biodistribution, and antitumor efficacy
    Moshikur RM, Ali MK, Wakabayashi R, Moniruzzaman M, Goto M
    Int J Pharm, 2021 Oct 25;608:121129.
    PMID: 34562557 DOI: 10.1016/j.ijpharm.2021.121129
    Oral delivery of the sparingly soluble drug methotrexate (MTX) is challenging owing to its poor bioavailability and low solubility. To address this challenge, the present study reports the conversion of MTX into a series of five ionic liquids (ILs) comprising a cationic component-i.e., cholinium (Cho), tetramethylammonium (TMA), tetrabutylphosphonium (TBP), or an amino acid ester-and an anionic component-i.e., MTX. The biocompatibility, pharmacokinetics, tissue distribution, and antitumor efficacy of each MTX-based IL were investigated to determine its usefulness as a pharmaceutical. Oral administration to mice revealed that proline ethyl ester MTX (IL[ProEt][MTX]) had 4.6-fold higher oral bioavailability than MTX sodium, followed by aspartic diethyl ester MTX, IL[TBP][MTX], IL[Cho][MTX], and IL[TMA][MTX]. The peak plasma concentration, elimination half-life, area under the plasma concentration, mean absorption time, and body clearance of IL[ProEt][MTX] were significantly (p 
    Matched MeSH terms: Tissue Distribution
  9. Fulltext Recent updates on liposomal formulations for detection, prevention and treatment of coronavirus disease (COVID-19)
    Dini Fatini Mohammad Faizal N, Cairul Iqbal Mohd Amin M
    Int J Pharm, 2023 Jan 05;630:122421.
    PMID: 36410670 DOI: 10.1016/j.ijpharm.2022.122421
    The unprecedented outbreak of severe acute respiratory syndrome-2 (SARS-CoV-2) worldwide has rendered it one of the most notorious pandemics ever documented in human history. As of November 2022, nearly 626 million cases of infection and over 6.6 million deaths have been reported globally. The scientific community has made significant progress in therapeutics and prevention for the management of coronavirus disease (COVID-19), including the development of vaccines and antiviral agents such as monoclonal antibodies and antiviral drugs. Although many advancements and a plethora of positive results have been obtained and global restrictions are being uplifted, obstacles in efficiently delivering these therapies, such as their rapid clearance, suboptimal biodistribution, and toxicity to organs, have yet to be addressed. To address these drawbacks, researchers have attempted applying nanotechnology-based formulations. Here, we summarized the recent data about COVID-19, its emergence, pathophysiology and life cycle, diagnosis, and currently-available medications. Subsequently, we discussed the progress in lipid nanocarriers, such as liposomes in infection detection and control. This review provides critical insights into the design of the latest liposomal-based formulations for tackling the barriers to detecting, preventing, and treating SARS-CoV-2.
    Matched MeSH terms: Tissue Distribution
  10. Pharmacokinetics of artemisinin-type compounds
    Navaratnam V, Mansor SM, Sit NW, Grace J, Li Q, Olliaro P
    Clin Pharmacokinet, 2000 Oct;39(4):255-70.
    PMID: 11069212
    Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.
    Matched MeSH terms: Tissue Distribution
  11. Background concentrations of Cd, Cu, Pb and Zn in the green-lipped mussel Perna viridis (Linnaeus) from Peninsular Malaysia
    Yap CK, Ismail A, Tan SG
    Mar Pollut Bull, 2003 Aug;46(8):1044-8.
    PMID: 12907200
    Matched MeSH terms: Tissue Distribution
  12. Synthesis and characterization of potential tumor scintigraphic agents
    Awaluddin AB, Jacobs JJ, Bourne DW, Maddalena DJ, Wilson JG, Boyd RE
    Int J Rad Appl Instrum A, 1987;38(8):671-4.
    PMID: 2822626
    Potential tumor imaging radiopharmaceutical agents have been prepared by attaching a cisplatin derivative to a ligand capable of forming a stable complex with 99mTc. Three new organometallic compounds, with iminodiacetic acid as the 99mTc chelating group and 2,3-diaminopropionamide as the platinum complexing group, have been prepared and characterized. Preliminary biodistribution studies in tumor bearing mice support the utility of this approach.
    Matched MeSH terms: Tissue Distribution
  13. Fulltext PET/CT analysis of 21 patients with breast cancer: physiological distribution of 18F-choline and diagnostic pitfalls
    Ahmad Saad FF, Zakaria MH, Appanna B
    J Int Med Res, 2018 Aug;46(8):3138-3148.
    PMID: 29781364 DOI: 10.1177/0300060518773019
    Objectives 18F-choline is a useful tracer for detecting tumours with high lipogenesis. Knowledge of its biodistribution pattern is essential to recognise physiological variants. The aim of this study was to describe the physiologic distribution of 18F-choline and pitfalls in patients with breast cancer. Methods Twenty-one consecutive patients with breast cancer (10 premenopausal and 11 postmenopausal women; mean age, 52.82 ± 10.71 years) underwent 18F-choline positron emission tomography (PET)/computed tomography (CT) for staging. Whole-body PET/CT was acquired after 40 minutes of 18F-choline uptake. Acquired PET images were measured semiquantitatively. Results All patients showed pitfalls unrelated to breast cancer. These findings were predominantly caused by physiological glandular uptake in the liver, spleen, pancreas, bowels, axial skeleton (85%-100%), inflammation and benign changes (4.76%), appendicular skeleton (4.76%-19.049%), and site contamination (61.9%). In <1%, a concomitant metastatic neoplasm was found. The breast showed higher physiological uptake in premenopausal compared with postmenopausal woman (18F-choline maximum standardised uptake values [g/dL] of the right breast = 2.04 ± 0.404 vs 1.59 ± 0.97 and left breast = 2.00 ± 0.56 vs 1.93 ± 1.28, respectively). Conclusion 18F-choline uptake was higher in premenopausal women. Physiological 18F-choline uptake was observed in many sites, representing possible pathologies.
    Matched MeSH terms: Tissue Distribution
  14. Fulltext Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
    Nurhidayah W, Widyasari EM, Daruwati I, Mahendra I, Subroto T, Khairul Ikram NK, et al.
    Int J Mol Sci, 2023 May 12;24(10).
    PMID: 37240025 DOI: 10.3390/ijms24108678
    The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.
    Matched MeSH terms: Tissue Distribution
  15. c(RGDfK) anchored surface manipulated liposome for tumor-targeted tyrosine kinase inhibitor (TKI) delivery to potentiate liver anticancer activity
    Deepak P, Kumar P, Arya DK, Pandey P, Kumar S, Parida BP, et al.
    Int J Pharm, 2023 Jul 25;642:123160.
    PMID: 37379892 DOI: 10.1016/j.ijpharm.2023.123160
    Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvβ3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.
    Matched MeSH terms: Tissue Distribution
  16. Vector-Mediated Cancer Gene Therapy Reduces Toxicity and Inhibition of Lung Carcinoma Growth in Nude Mice
    Khalaf AT, Wan J, Wei H, Fubing S, Zainol J, Kadir SYA, et al.
    Appl Biochem Biotechnol, 2024 Jan;196(1):261-274.
    PMID: 37119504 DOI: 10.1007/s12010-023-04463-4
    Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all.
    Matched MeSH terms: Tissue Distribution
  17. Uptake and clearance analysis of Technetium99m labelled iron oxide nanoparticles in a rabbit brain
    Nadeem M, Ahmad M, Saeed MA, Shaari A, Riaz S, Naseem S, et al.
    IET Nanobiotechnol, 2015 Jun;9(3):136-41.
    PMID: 26023157 DOI: 10.1049/iet-nbt.2014.0012
    Nanoparticles as solid colloidal particles are extensively studied and used as anticancer drug delivery agents because of their physical properties. This current research aims to prepare water base suspension of uncoated iron oxide nanoparticles and their biodistribution study to different organs, especially the brain, by using a single photon emission computed tomography gamma camera. The water-based suspension of iron oxide nanoparticles was synthesised by a reformed version of the co-precipitation method and labelled with Tc99m for intravenous injection. The nanoparticles were injected without surface modification. X-ray diffraction (XRD), energy dispersive spectrometry (EDS) and transmission electron microscope (TEM) techniques were used for characterisation. Peaks of XRD and EDS indicate that the particles are magnetite and exist in aqueous suspension. The average diameter of iron oxide nanoparticles without any surface coating determined by TEM is 10 nm. These particles are capable of evading the reticuloendothelial system and can cross the blood-brain barrier in the rabbit. The labelling efficiency of iron oxide nanoparticles labelled with Tc99m is 85%, which is good for the biodistribution study. The sufficient amount of iron oxide nanoparticles concentration in the brain as compared with the surrounding soft tissues and their long blood retention time indicates that the water-based suspension of iron oxide nanoparticles may be an option for drug delivery into the brain.
    Matched MeSH terms: Tissue Distribution
  18. Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron improve antitumor efficacy: In vitro and in vivo studies
    Voon SH, Kue CS, Imae T, Saw WS, Lee HB, Kiew LV, et al.
    Int J Pharm, 2017 Dec 20;534(1-2):136-143.
    PMID: 29031979 DOI: 10.1016/j.ijpharm.2017.10.023
    Previously reported amphiphilic diblock copolymer with pendant dendron moieties (P71D3) has been further evaluated in tumor-bearing mice as a potential drug carrier. This P71D3-based micelle of an average diameter of 100nm was found to be biocompatible, non-toxic and physically stable in colloidal system up to 15days. It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing mice, the tumor growth rate of P71D3/DOX (2mg/kg DOX equivalent) treated group was significantly delayed and their tumor volume was significantly reduced by 1.5-fold compared to those treated with free DOX. The biodistribution studies indicated that P71D3/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold higher than free DOX treated mice at 15min and 1h post-administration, respectively. These results suggest that P71D3 micelle is a promising nanocarrier for chemotherapeutic agents.
    Matched MeSH terms: Tissue Distribution/drug effects
  19. Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice
    Soo GW, Law JH, Kan E, Tan SY, Lim WY, Chay G, et al.
    Anticancer Drugs, 2010 Aug;21(7):695-703.
    PMID: 20629201
    Imatinib, a selective inhibitor of c-KIT and Bcr-Abl tyrosine kinases, approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, shows further therapeutic potential for gliomas, glioblastoma, renal cell carcinoma, autoimmune nephritis and other neoplasms. It is metabolized by CYP3A4, is highly bound to alpha-1-acid glycoprotein and is a P-glycoprotein substrate limiting its brain distribution. We assess imatinib's protein binding interaction with primaquine, which also binds to alpha-1-acid glycoprotein, and its metabolic interaction with ketoconazole, which is a CYP3A4 inhibitor, on its pharmacokinetics and biodistribution. Male ICR mice, 9-12 weeks old were given imatinib PO (50 mg/kg) alone or co-administered with primaquine (12.5 mg/kg), ketoconazole (50 mg/kg) or both, and imatinib concentration in the plasma, kidney, liver and brain was measured at prescheduled time points by HPLC. Noncompartmental pharmacokinetic parameters were estimated. Primaquine increased 1.6-fold plasma AUC(0)--> infinity, C(Max) decreased 24%, T(Max) halved and t(1/2) and mean residence time were longer. Ketoconazole increased plasma AUC(0)-->infinity 64% and doubled the C(Max), but this dose did not affect t(1/2) or mean residence time. When ketoconazole and primaquine were co-administered, imatinib AUC(0)-->infinity and C(Max) increased 32 and 35%, respectively. Ketoconazole did not change imatinib's distribution efficiency in the liver and kidney, primaquine increased it two-fold and it was larger when both the drugs were co-administered with imatinib. Ketoconazole did not change brain penetration but primaquine increased it approximately three-fold. Ketoconazole and primaquine affect imatinib clearance, bioavailability and distribution pattern, which could improve the treatment of renal and brain tumors, but also increase toxicity. This would warrant hepatic and renal functions monitoring.
    Matched MeSH terms: Tissue Distribution/drug effects
  20. Similarities and differences of metal distributions in the tissues of molluscs by using multivariate analyses
    Yap CK, Edward FB, Tan SG
    Environ Monit Assess, 2010 Jun;165(1-4):39-53.
    PMID: 19452255 DOI: 10.1007/s10661-009-0925-6
    Multivariate analysis including correlation, multiple stepwise linear regression, and cluster analyses were applied to investigate the heavy metal concentrations (Cd, Cu, Fe, Ni, Pb, and Zn) in the different parts of bivalves and gastropods. It was also aimed to distinguish statistically the differences between the marine bivalves and the gastropods with regards to the accumulation of heavy metals in the different tissues. The different parts of four species of bivalves and four species of gastropods were obtained and analyzed for heavy metals. The multivariate analyses were then applied on the data. From the multivariate analyses conducted, there were correlations found between the soft tissues of bivalves and gastropods, but none was found between the shells and the soft tissues of most of the molluscs (except for Cerithidea obtusa and Puglina cochlidium). The significant correlations (P < 0.05) found between the soft tissues were further complemented by the multiple stepwise linear regressions where heavy metals in the total soft tissues were influenced by the accumulation in the different types of soft tissues. The present study found that the distributions of heavy metals in the different parts of molluscs were related to their feeding habits and living habitats. The statistical approaches proposed in this study are recommended for use in biomonitoring studies, since multivariate analyses can reduce the cost and time involved in identifying an effective tissue to monitor the heavy metal(s) bioavailability and contamination in tropical coastal waters.
    Matched MeSH terms: Tissue Distribution
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