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Levels of heavy metals in green-lipped mussel Perna veridis (Linnaeus) from Muar Estuary, Johore, Malaysia

Kamaruzzaman BY, Ong MC, Zaleha K, Shahbudin S

Pak J Biol Sci, 2008 Sep 15;11(18):2249-53.
PMID: 19137835

Muscle and feather in tissue of 40 juveniles and 40 adult green-lipped mussel Perna veridis (L.) collected from Muar Estuary, Johor were analyzed for copper (Cu), cadmium (Cd), lead (Pb) and zinc (Zn) concentration using a fast and sensitive Inductively Coupled Plasma Mass Spectrometer (ICP-MS). In this study, the average concentration of Cu was 8.96 microg g(-1) dry weights, Cd with 0.58 microg g(-1) dry weight, Pb averaging 2.28 microg g(-1) dry weights and Zn averaged to 86.73 microg g(-1) dry weight. The highest accumulation of metal studied was found in feather sample compared to the muscle. The positive relationship of Cu, Cd, Pb and Zn with P. virdis length suggesting that the accumulation of these metals were formed in the mussel. In all cases, metal levels found were lower than the guideline of international standards of reference and the examined bivalve were not associated with enhanced metal content in their tissues and were safe within the limits for human consumption.

Matched MeSH terms: Tissue Distribution
Oxygen demand, nitrogen and copper removal by free-water-surface and subsurface-flow constructed wetlands under tropical conditions

Lim PE, Wong TF, Lim DV

Environ Int, 2001 May;26(5-6):425-31.
PMID: 11392762

This study was conducted to: (1) assess the role of wetland vegetation in the removal of oxygen demand and nitrogen under tropical conditions, (2) estimate the uptake of nitrogen and copper by wetland plants and (3) investigate the speciation of Cu in wetland media among four operationally defined host fractions, namely exchangeable, carbonate, reducible and organically bound. Four laboratory-scale wetland units, two free-water-surface (FWS) and two subsurface-flow (SF) with one of each planted with cattails (Typha augustifolia), were fed with primary-treated sewage and operated at nominal retention times of 0.6-7 days. The influent and effluent BOD/COD and nitrogen concentrations were monitored to assess the performance of the wetland units for various mass loading rates. At the end of the study, all cattail plants were harvested and analyzed for total Kjeldahl nitrogen (TKN). Four other wetland units, which were identical to the first four, were fed with domestic wastewater spiked with copper in increasing concentrations. Copper speciation patterns in the sand layer were determined at the end of the study. The results showed that wetland vegetation did not play an important role in oxygen demand removal but were capable of removing about 22% and 26% of the nitrogen input in the FWS and SF wetland units, respectively. Mass balance analysis indicated that less than 1% of copper introduced was taken up by the cattails. Copper speciation patterns in the sand media showed that the exchangeable fraction contributed 30-57% and 63-80% of the nonresidual copper in the planted and unplanted FWS wetlands, respectively. For SF units, the percentages were 52-62% and 59-67%, respectively. This indicates that large amount of copper in the media were potentially remobilizable.

Matched MeSH terms: Tissue Distribution
Fulltext Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Roselt P, Cullinane C, Noonan W, Elsaidi H, Eu P, Wiebe LI

Molecules, 2020 Dec 03;25(23).
PMID: 33287202 DOI: 10.3390/molecules25235700

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E's biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.

Matched MeSH terms: Tissue Distribution/physiology*
Fulltext Gene expression changes in spleens and livers of tumour-bearing mice suggest delayed inflammation and attenuated cachexia in response to oil palm phenolics

Leow SS, Sekaran SD, Sundram K, Tan Y, Sambanthamurthi R

J Nutrigenet Nutrigenomics, 2013;6(6):305-26.
PMID: 24642698 DOI: 10.1159/000357948

Plant phenolics can inhibit, retard or reverse carcinogenesis, and may thus help prevent or treat cancer. Oil palm phenolics (OPP) previously showed anti-tumour activities in vivo via a cytostatic mechanism at 1,500 ppm gallic acid equivalent. Here, we report other possible molecular mechanisms by which this extract attenuates cancer, especially those concerning the immune response.

Matched MeSH terms: Tissue Distribution
Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery

Wong TW

J Control Release, 2014 Nov 10;193:257-69.
PMID: 24801250 DOI: 10.1016/j.jconrel.2014.04.045

Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described.

Matched MeSH terms: Tissue Distribution
Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate

Charoo NA, Shamsher AA, Lian LY, Abrahamsson B, Cristofoletti R, Groot DW, et al.

J Pharm Sci, 2014 Feb;103(2):378-91.
PMID: 24382794 DOI: 10.1002/jps.23817

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8.

Matched MeSH terms: Tissue Distribution
Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice

Nograles N, Abdullah S, Shamsudin MN, Billa N, Rosli R

J Biosci Bioeng, 2012 Feb;113(2):133-40.
PMID: 22093752 DOI: 10.1016/j.jbiosc.2011.10.003

Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 μm±3.07 μm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 μg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 μg, 100 μg and 150 μg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (<1.0%) with 1.3-fold higher levels for the 100 μg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination.

Matched MeSH terms: Tissue Distribution
Development of gelatin microspheres loaded with diclofenac sodium for intra-articular administration

Saravanan M, Bhaskar K, Maharajan G, Pillai KS

J Drug Target, 2011 Feb;19(2):96-103.
PMID: 20380621 DOI: 10.3109/10611861003733979

We have previously reported on the targeting of diclofenac sodium in joint inflammation using gelatin magnetic microspheres. To overcome complications in the administration of magnetic microspheres and achieve higher targeting efficiency, the present work focuses on the formulation of gelatin microspheres for intra-articular administration. Drug-loaded microspheres were prepared by the emulsification/cross-linking method, characterized by drug loading, size distribution, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gas chromatography, and in vitro release studies. The targeting efficiency of microspheres was studied in vivo in rabbits. The microspheres showed drug loading of 9.8, 18.3, and 26.7% w/w with an average size range of 37-46 µm, depending upon the drug-polymer ratio. They were spherical in nature and free from surface drug as evidenced by the SEM photographs. FT-IR, DSC, and XRD revealed the absence of drug-polymer interaction and amorphous nature of entrapped drug. Gas chromatography confirms the absences of residual glutaraldehyde. The formulated microspheres could prolong the drug release up to 30 days in vitro. About 81.2 and 43.7% of administered drug in the microspheres were recovered from the target joint after 1 and 7 days of postintra-articular injection, respectively, revealing good targeting efficiency.

Matched MeSH terms: Tissue Distribution
HPLC determination of imatinib in plasma and tissues after multiple oral dose administration to mice

Teoh M, Narayanan P, Moo KS, Radhakrisman S, Pillappan R, Bukhari NI, et al.

Pak J Pharm Sci, 2010 Jan;23(1):35-41.
PMID: 20067864

Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases. It is approved for the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST) and has further therapeutic potential. Male ICR mice were given imatinib PO (50 or 25 mg/kg, 5 doses every 2 h); euthanized 2 h after the last dose administration; plasma, liver, brain, spleen and kidney were collected and imatinib concentration measured by an optimized HPLC method for quantification in tissues. Methanol (1:1 v/v plasma) and pH 4, 40:30:30 (v/v/v) water-methanol-acetonitrile at 5 ml/g (brain) and 10 ml/g (spleen, kidney, liver) ratio was added to the samples, homogenized, sonicated, centrifuged (15,000 rpm, 5 min, 2 degrees C) and the supernatant injected into an Inertsil CN-3 column (4.6 mm x 150 mm, 5 microm) using 64:35:1 (v/v/v) water-methanol-triethylamine (pH 4.8), flow rate 1 ml/min, 25 degrees C. Imatinib eluted at 7.5 min (268 nm). Linearity: 0.1-50 microg/ml; precision, accuracy, inter- and intra-day variability was within 15%. Recovery was above 95% (plasma), 80% (brain) and 90% (kidney, liver, spleen). Imatinib tissue concentrations were 6-8 folds higher than plasma except brain, where the ratio decreased from 0.24 to 0.08 suggesting limited brain penetration, likely due to blood brain barrier efflux transporters. The extensive distribution supports the expansion of therapeutic applications.

Matched MeSH terms: Tissue Distribution
Telescopium telescopium as potential biomonitors of Cu, Zn, and Pb for the tropical intertidal area

Yap CK, Noorhaidah A, Azlan A, Nor Azwady AA, Ismail A, Ismail AR, et al.

Ecotoxicol Environ Saf, 2009 Feb;72(2):496-506.
PMID: 18243309 DOI: 10.1016/j.ecoenv.2007.12.005

The distributions of Cu, Zn, and Pb concentrations in the selected soft tissues (foot, cephalic tentacle, mantle, muscle, gill, digestive caecum, and remaining soft tissues) and shells of the mud-flat snail Telescopium telescopium were determined in snails from eight geographical sites in the south-western intertidal area of Peninsular Malaysia. Generally, the digestive caecum compared with other selected soft tissues, accumulated higher concentration of Zn (214.35+/-14.56 microg/g dry weight), indicating that the digestive caecum has higher affinity for the essential Zn to bind to metallothionein. The shell demonstrated higher concentrations of Pb (41.23+/-1.20 microg/g dry weight) when compared to the selected soft tissues except gill from Kuala Sg. Ayam (95.76+/-5.32 microg/g dry weight). The use of different soft tissues also can solve the problem of defecation to reduce error in interpreting the bioavailability of heavy metals in the intertidal area.

Matched MeSH terms: Tissue Distribution
A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats

Tanvir EM, Afroz R, Chowdhury M, Gan SH, Karim N, Islam MN, et al.

Hum Exp Toxicol, 2016 Sep;35(9):991-1004.
PMID: 26519480 DOI: 10.1177/0960327115614384

This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.

Matched MeSH terms: Tissue Distribution
Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics

Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.

Curr Drug Deliv, 2015;12(6):795-804.
PMID: 26324229

Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.

Matched MeSH terms: Tissue Distribution
Fulltext Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats

Zakarial Ansar FH, Latifah SY, Wan Kamal WHB, Khong KC, Ng Y, Foong JN, et al.

Int J Nanomedicine, 2020;15:7703-7717.
PMID: 33116496 DOI: 10.2147/IJN.S262395

Background: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs.
Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.
Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.
Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.

Matched MeSH terms: Tissue Distribution
Fulltext Preparation, Characterization, and Radiolabeling of [68Ga]Ga-NODAGA-Pamidronic Acid: A Potential PET Bone Imaging Agent

Ashhar Z, Yusof NA, Ahmad Saad FF, Mohd Nor SM, Mohammad F, Bahrin Wan Kamal WH, et al.

Molecules, 2020 Jun 09;25(11).
PMID: 32526838 DOI: 10.3390/molecules25112668

Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of image-guided radiopharmaceuticals are being employed as an alternative to traditional biopsies. Hence, in the present work, we tested the efficacy of a gallium-68 (68Ga)-based compound as a radiopharmaceutical agent towards the bone imaging in positron emitting tomography (PET). For that, we prepared, thoroughly characterized, and radiolabeled [68Ga]Ga-NODAGA-pamidronic acid radiopharmaceutical, a 68Ga precursor for PET bone cancer imaging applications. The preparation of NODAGA-pamidronic acid was performed via the N-Hydroxysuccinimide (NHS) ester strategy and was characterized using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MSn). The unreacted NODAGA chelator was separated using the ion-suppression reverse phase-high performance liquid chromatography (RP-HPLC) method, and the freeze-dried NODAGA-pamidronic acid was radiolabeled with 68Ga. The radiolabeling condition was found to be most optimum at a pH ranging from 4 to 4.5 and a temperature of above 60 °C. From previous work, we found that the pamidronic acid itself has a good bone binding affinity. Moreover, from the analysis of the results, the ionic structure of radiolabeled [68Ga]Ga-NODAGA-pamidronic acid has the ability to improve the blood clearance and may exert good renal excretion, enhance the bone-to-background ratio, and consequently the final image quality. This was reflected by both the in vitro bone binding assay and in vivo animal biodistribution presented in this research.

Matched MeSH terms: Tissue Distribution
Favipiravir-Based Ionic Liquids as Potent Antiviral Drugs for Oral Delivery: Synthesis, Solubility, and Pharmacokinetic Evaluation

Moshikur RM, Ali MK, Wakabayashi R, Moniruzzaman M, Goto M

Mol Pharm, 2021 08 02;18(8):3108-3115.
PMID: 34250805 DOI: 10.1021/acs.molpharmaceut.1c00324

Coronavirus disease 2019 (COVID-19) has spread across the world, and no specific antiviral drugs have yet been approved to combat this disease. Favipiravir (FAV) is an antiviral drug that is currently in clinical trials for use against COVID-19. However, the delivery of FAV is challenging because of its limited solubility, and its formulation is difficult with common organic solvents and water. To address these issues, four FAV ionic liquids (FAV-ILs) were synthesized as potent antiviral prodrugs and were fully characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectrometry, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), derivative thermogravimetry (DTG), and differential scanning calorimetry (DSC). The aqueous solubility and in vivo pharmacokinetic properties of the FAV-ILs were also evaluated. The FAV-ILs exhibited improved aqueous solubility by 78 to 125 orders of magnitude when compared with that of free FAV. Upon oral dosing in mice, the absolute bioavailability of the β-alanine ethyl ester FAV formulation was increased 1.9-fold compared with that of the control FAV formulation. The peak blood concentration, elimination half-life, and mean absorption time of FAV were also increased by 1.5-, 2.0-, and 1.5-fold, respectively, compared with the control. Furthermore, the FAV in the FAV-ILs exhibited significantly different biodistribution compared with the control FAV formulation. Interestingly, drug accumulation in the lungs and liver was improved 1.5-fold and 1.3-fold, respectively, compared with the control FAV formulation. These results indicate that the use of ILs exhibits potential as a simple, scalable strategy to improve the solubility and oral absorption of hydrophobic drugs, such as FAV.

Matched MeSH terms: Tissue Distribution
Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats

Tan JSL, Roberts C, Billa N

J Biomater Sci Polym Ed, 2020 02;31(2):141-154.
PMID: 31612804 DOI: 10.1080/09205063.2019.1680926

Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.

Matched MeSH terms: Tissue Distribution
Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials

Tiede A, Abdul-Karim F, Carcao M, Persson P, Clausen WHO, Kearney S, et al.

Haemophilia, 2017 Jul;23(4):547-555.
PMID: 28233381 DOI: 10.1111/hae.13191

INTRODUCTION: Nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (FIX) with an extended half-life developed for routine prophylaxis and the prevention and treatment of bleeding episodes in patients with haemophilia B.
AIM: The aim of this study was to evaluate the pharmacokinetics (PK) of N9-GP.
METHODS: Data from 41 previously treated haemophilia B patients, enrolled globally (16 adolescents/adults and 25 children; FIX activity ≤0.02 IU mL-1) with no history of FIX inhibitors, were included. N9-GP was administered once-weekly as 10 IU kg-1or 40 IU kg-1in adolescents/adults and 40 IU kg-1in children. Blood was sampled up to 168 h (1 week) post dose. Standard PK was estimated on the basis of plasma FIX activity vs. time (PK profiles) using non-compartmental methods. Furthermore, a population PK analysis and FIX activity predictions were performed.
RESULTS: Incremental recoveries were 0.02 (IU mL-1)/(IU kg-1) in both adolescents/adults and children. The extended half-life resulted in mean trough levels of 0.27 IU mL-1for adolescents/adults and 0.17 IU mL-1for children at steady-state after weekly dosing at 40 IU kg-1. The population PK analysis confirmed a mono-exponential decay in FIX activity and allowed for predictions of FIX activity for adolescents/adults above 0.15 IU mL-1at all times and 6.4 days week-1in children.
CONCLUSION: N9-GP has the potential to shift previously treated haemophilia B patients from a severe/moderate disease state into a mild- or non-haemophilic range for most of the dosing interval, which is expected to reduce the number of bleeding episodes.

Matched MeSH terms: Tissue Distribution
Can the byssus of green-lipped mussel Perna viridis (Linnaeus) from the west coast of Peninsular Malaysia be a biomonitoring organ for Cd, Pb and Zn? Field and laboratory studies

Yap CK, Ismail A, Tan SG

Environ Int, 2003 Jul;29(4):521-8.
PMID: 12705949

Concentrations of cadmium (Cd), lead (Pb) and zinc (Zn) in total soft tissues (ST) and byssus (BYS) of the green-lipped mussel Perna viridis from 11 different geographical locations off the west coast of Peninsular Malaysia were determined. The metal concentrations distributed between the BYS and ST were compared. The results of this study indicated that higher levels of Cd (1.31 microg/g), Pb (38.49 microg/g) and Zn (206.52 microg/g) were accumulated in the BYS than in the total ST (Cd: 0.29 microg/g; Pb: 8.27 microg/g; Zn: 102.6 microg/g). Semi-static and short period controlled laboratory experiments were also conducted for the accumulation and depuration of Cd, Pb and Zn in the total ST and BYS of P. viridis. The ratios (BYS/ST) for Pb and Cd from the laboratory experiments showed that the total ST accumulated more metals than the BYS. Therefore, these laboratory results disagreed with those found for the field samples. However, the laboratory results for the Zn ratio (BYS/ST) agreed with those of the field samples. It was evident that when compared to the ST, the BYS was a more sensitive biomonitoring organ for Zn while it could be a complementary organ for Cd and Pb in the total ST. Since total ST of P. viridis had been reported to have regulative mechanism for Zn, its BYS can be used as a biomonitoring organ for the identification of coastal areas exposed to Zn pollution.

Matched MeSH terms: Tissue Distribution
Correlations between speciation of Cd, Cu, Pb And Zn in sediment and their concentrations in total soft tissue of green-lipped mussel Perna viridis from the west coast of Peninsular Malaysia

Yap CK, Ismail A, Tan SG, Omar H

Environ Int, 2002 Apr;28(1-2):117-26.
PMID: 12046948

Total concentrations and speciation of cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) in surface sediment samples were correlated with the respective metal measured in the total soft tissue of the green-lipped mussel Perna viridis, collected from water off the west coast of Peninsular Malaysia. The aim of this study is to relate the possible differences in the accumulation patterns of the heavy metals in P. viridis to those in the surface sediment. The sequential extraction technique was employed to fractionate the sediment into 'freely leachable and exchangeable' (EFLE), 'acid-reducible,' 'oxidisable-organic' and 'resistant' fractions. The results showed that significant (P .05) was found between Zn in P viridis and all the sediment geochemical fractions of Zn and total Zn in the sediment. This indicated that Zn was possibly regulated from the soft tissue of P. viridis. The present results supported the use of P viridis as a suitable biomonitoring agent for Cd, Cu and Pb.

Matched MeSH terms: Tissue Distribution
Fulltext Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities

Ruman U, Fakurazi S, Masarudin MJ, Hussein MZ

Int J Nanomedicine, 2020;15:1437-1456.
PMID: 32184597 DOI: 10.2147/IJN.S236927

The development of therapeutics and theranostic nanodrug delivery systems have posed a challenging task for the current researchers due to the requirement of having various nanocarriers and active agents for better therapy, imaging, and controlled release of drugs efficiently in one platform. The conventional liver cancer chemotherapy has many negative effects such as multiple drug resistance (MDR), high clearance rate, severe side effects, unwanted drug distribution to the specific site of liver cancer and low concentration of drug that finally reaches liver cancer cells. Therefore, it is necessary to develop novel strategies and novel nanocarriers that will carry the drug molecules specific to the affected cancerous hepatocytes in an adequate amount and duration within the therapeutic window. Therapeutics and theranostic systems have advantages over conventional chemotherapy due to the high efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimum side effects. These nanocarriers possess high drug accumulation in the tumor area while minimizing toxic effects on healthy tissues. This review focuses on the current research on nanocarrier-based therapeutics and theranostic drug delivery systems excluding the negative consequences of nanotechnology in the field of drug delivery systems. However, clinical developments of theranostics nanocarriers for liver cancer are considered outside of the scope of this article. This review discusses only the recent developments of nanocarrier-based drug delivery systems for liver cancer therapy and diagnosis. The negative consequences of individual nanocarrier in the drug delivery system will also not be covered in this review.

Matched MeSH terms: Tissue Distribution

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