Biodistribution study of free and microencapsulated 6‐methylcoumarin in Wistar rats by HPLC

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6‐methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C₁₈ column was used with UV detection at 321 nm and a gradient system consisting of methanol‐deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r² > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4–12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC‐free and 6MC‐loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC‐free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and characterization of 7-(CH3)3N-4- {2,4-(NO2)2C6H3S}-nido-7-CB10H11 and its Biodistribution in C57B16 Mice Bearing B16 Melanoma

7-(CH₃)₃N-4-{2,4-(NO₂)₂C₆H₃S}-nido-7-CB₁₀H₁₁ has been synthesized through a Friedel-Crafts substitution reaction on 7-(CH₃)3N-nido-7- CB₁₀H₁₂. A biodistribution study in mice with implanted B16 melanoma indicates that the compound locates in neoplastic tissue at concentrations which suggest that its use in ¹⁰B neutron capture therapy may be feasible.     

Determination of 3-chloro-1,2-propanediol in biological samples by quick-easy-cheap-effective-rugged-and-safe extraction coupled with gas chromatography-mass spectrometry and its biodistribution in rats

3-Chloro-1,2-propanediol is a common food contaminant, but reports on its determination in biological tissues are lacking. In the present study, a method was developed to detect 3-chloro-1,2-propanediol contents in rat tissues by quick-easy-cheap-effective-rugged-and-safe extraction and gas chromatography-mass spectrometry analysis. Biological samples were extracted with ethyl acetate and purified with adsorbents. The optimized adsorbent for each sample was selected from 4–5 combinations of N-propylethylenediamine, octadecylsilane, graphitized carbon black, strong anion exchange, and florisil. Extracted 3-chloro-1,2-propanediol was derivatized with heptafluorobutyric anhydride and subjected to gas chromatography-mass spectrometry. This method had good linearity (correlation coefficients >0.99) in the range of 2–2000 ng/g for blood, kidney, liver, testis, and brain samples. The limits of detection were under 0.8 ng/g; the limits of quantification were 2 ng/g; the recovery rates were 85%–102%; and the matrix effects were 1.98%–7.67%. This method also had good precision. The dynamic changes in 3-chloro-1,2-propanediol in rats gavaged with 20 mg/kg b.w. for 24 h were detected using this method. The 3-chloro-1,2-propanediol content in each tissue sharply increased to a peak, rapidly decreased within 2 h, and stabilized at 12 h. 3-Chloro-1,2-propanediol persisted in the kidney, testis, and liver 24 h after gavage.     

A Supramolecular Approach for Preparation of Size‐Controlled Nanoparticles

A supramolecular approach has been developed for the preparation of supramolecular nanoparticles (SNPs) with variable sizes (30–450 nm) from three different molecular building blocks using a cyclodextrin/adamantane recognition system. Positron emission tomography (PET) was employed to study the biodistribution and lymph node drainage of the SNPs in mice. The sizes of the SNPs affect their in vivo characteristics (see picture).

     

Systemic Administration of Polymer‐Coated Nano‐Graphene to Deliver Drugs to Glioblastoma

Graphene—2D carbon—has received significant attention thanks to its electronic, thermal, and mechanical properties. Recently, nano‐graphene (nGr) has been investigated as a possible platform for biomedical applications. Here, a polymer‐coated nGr to deliver drugs to glioblastoma after systemic administration is reported. A biodegradable, biocompatible poly(lactide) (PLA) coating enables encapsulation and controlled release of the hydrophobic anticancer drug paclitaxel (PTX), and a hydrophilic poly(ethylene glycol) (PEG) shell increases the solubility of the nGr drug delivery system. Importantly, the polymer coating mediates the interaction of nGr with U‐138 glioblastoma cells and decreases cytotoxicity compared with pristine untreated nGr. PLA‐PEG‐coated nGr is also able to encapsulate PTX at 4.15 wt% and sustains prolonged PTX release for at least 19 d. PTX‐loaded nGr‐PLA‐PEGs are shown to kill up to 20% of U‐138 glioblastoma cells in vitro. Furthermore, nGr‐PLA‐PEG and CNT‐PLA‐PEG, two carbon nanomaterials with different shapes, are able to kill U‐138 in vitro as well as free PTX at significantly lower doses of drug. Finally, in vivo biodistribution of nGr‐PLA‐PEG shows accumulation of nGr in intracranial U‐138 glioblastoma xenografts and organs of the reticuloendothelial system.     

LC‐MS/MS for Determination of Paclitaxel in Rat Tissues: Application to a Biodistribution Study of Paclitaxel Nanoliposome Modified by PEO‐PPO‐PEO Triblock Copolymers

Abstract

A liquid chromatography‐tandem triple‐quadrupole mass spectrometry assay to quantify palitaxel in rat tissue homogenates containing paclitaxel nanoliposome (PTX‐NLP) modified by PEO-PPO-PEO triblock copolymers was developed and validated. Liquid–liquid extraction with tert‐butyl methyl ether was used for preparation of tissue samples and docetaxel was used as the internal standard. Paclitaxel and docetaxel were separated on a 200 mm×4.6 mm×5 µm C₁₈ column and quantified using a triple‐quadrupole mass spectrometer operating in positive ion electrospray selective reaction monitoring mode (ESI⁺‐SRM) with a total run time of 6.0 min. The peak area of the m/z 876.3→307.9 transition of paclitaxel is measured vs. that of the m/z 830.3→549.1 transition of docetaxel to generate the standard curves. The standard curves were linear over the concentration range of 0.2–2000 ng/mL for different tissues. The method had high extraction recovery (>90%) and accuracy (>90%) with the intraday and inter‐day precision <15%. Frozen stability, freeze‐thaw stability, extracted stability, and solution stability under ambient temperature were examined, which indicated the tissue samples should be extracted within 5 days and avoid being frozen and thawed repeatedly over 5 times, extracted samples after evaporation could be stored at ?20°C for 20 days without drug degradation, also, no degradation was observed after solution samples were left out at ambient temperature for 24 h. This assay was used to support an in vivo biodistribution study of paclitaxel nanoliposome modified by PEO-PPO-PEO triblock copolymers in rats.     

Studies of the uranium biodistribution in animals contaminated by ingestion using fission track method

Using animals a study on the internal contamination by U ingestion is presented. Two rats of Wistar-London breed were contaminated at once and after different time intervals, 3 days and 10 days respectively, they were sacrified. Uranium biodistribution in the vital organs as well as the uranium retention and elimination was investigated using the fission track method. For the two contaminated subjects a comparison between obtained quantitative results is given.     

Preclinical Assessment Addressing Intravenous Administration of a [68Ga]Ga-PSMA-617 Microemulsion: Acute In Vivo Toxicity,Tolerability, PET Imaging,and Biodistribution

It has been herein presented that a microemulsion, known to be an effective and safe drug delivery system following intravenous administration, can be loaded with traces of [⁶⁸Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability of the microemulsion in altering [⁶⁸Ga]Ga-PSMA-617 distribution was presented at 120 min post injection based on its ex vivo biodistribution results.     

Fluorescence‐Labeled Immunomicelles: Preparation,in vivo Biodistribution,and Ability to Cross the Blood–Brain Barrier

Multifunctional hybrid micelles are prepared from amphiphilic mal‐PEG‐b‐PLA and mPEG‐b‐P(LA‐co‐DHC/RhB) block copolymers. A specific anti‐transferrin receptor antibody, OX26, is linked onto the surface of the micelles. ELISA indicates that the conjugated antibody preserves its activity. OX26 conjugation can increase the uptake efficiency of micelles by target cell lines (C6). Pharmacokinetics and in vivo biodistribution experiments are carried out to investigate the ability of OX26‐conjugated micelles (immunomicelles) to cross the blood–brain barrier. The data show that the brain uptake of OX26‐conjugated micelles is much more than that of OX26‐free ones. Therefore, OX26‐conjugated micelles will be promising drug carriers to cross the blood‐brain barrier.

     

Prostate‐Cancer‐Targeted N‐(2‐Hydroxypropyl)methacrylamide Copolymer/Docetaxel Conjugates

Biodistribution, pharmacokinetics, and efficacy of prostate‐cancer‐targeted HPMA copolymer/DTX conjugates are evaluated in nude mice bearing prostate cancer C4‐2 xenografts. PSMA‐specific monoclonal antibodies 3F/11 are used as the targeting moiety. Control conjugates contain either non‐specific IgG or no IgG. The ratios of tumor accumulation to total background organs (heart, lung, kidney, liver, spleen and blood) accumulation increase substantially with time for the targeted conjugate, and the ratio at 48 h is 7‐fold higher than that at 6 h. Preliminary evaluation of the efficacy of the conjugates in vivo show tumor growth inhibition for all HPMA copolymer/DTX conjugates.