Evidence map›Paper›PMID 39700200›Full record

ArticlePloS one2024

In vivo imaging and pharmacokinetics of percutaneously injected ultrasound and X-ray imageable thermosensitive hydrogel loaded with doxorubicin versus free drug in swine.

Jose F Delgado, Ayele H Negussie, Nicole A Varble, Andrew S Mikhail, Antonio Arrichiello, Tabea Borde, Laetitia Saccenti, Ivane Bakhutashvili, Joshua W Owen, Robert Morhard and 3 more

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

13 authors.

Jose F DelgadoCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0009-0001-8495-2783
Ayele H NegussieCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Nicole A VarbleCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0000-0003-2273-7962
Andrew S MikhailCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Antonio ArrichielloCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Tabea BordeCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Laetitia SaccentiCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0000-0002-9765-0039
Ivane BakhutashviliCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Joshua W OwenCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Robert MorhardCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
John W KaranianCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
William F PritchardCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0000-0001-5805-5344
Bradford J WoodCenter for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.

Funding

Center for Interventional OncologyZIDBC011242 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WOOD, BRADFORD J · 2009 to 2025
$18.7M
Intramural NIH HHS ZID BC011242
6 · The paper itself

Abstract

Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region. Secondly, pharmacokinetics of POL loaded with doxorubicin (POLDOX) were evaluated and compared to free doxorubicin injection (DOXSoln) with a Single End Hole Needle. Utilizing 2D and 3D morphometrics from US and x-ray imaging techniques such as Computed Tomography (CT) and Cone Beam CT (CBCT), we monitored the localization and leakage of POLDOX over time. Relative iodine concentrations measured with CBCT following incorporation of an iodinated contrast agent in POL indicated potential drug diffusion and advection transport. Furthermore, US imaging revealed temporal changes, suggesting variations in acoustic intensity, heterogeneity, and echotextures. Notably, 3D reconstruction of the distribution of POL and POLDOX from 2D ultrasound frames was achieved and morphometric data obtained. Pharmacokinetic analysis revealed lower systemic exposure of the drug in various organs with POLDOX formulation compared to DOXSoln formulation. This was demonstrated by a lower area under the curve (852.1 ± 409.1 ng/mL·h vs 2283.4 ± 377.2 ng/mL·h) in the plasma profile, suggesting a potential reduction in systemic toxicity. Overall, the use of POL formulation offers a promising strategy for precise and localized drug delivery, that may minimize adverse effects. Dual modality POL imaging enabled analysis of patterns of gel distribution and morphology, alongside of pharmacokinetics of local delivery. Incorporating hydrogels into drug delivery systems holds significant promise for improving the predictability of the delivered drug and enhancing spatial conformability. These advancements can potentially enhance the safety and precision of anticancer therapy.

Indexed as

DoxorubicinHydrogelsAnimalsAntibiotics, AntineoplasticCone-Beam Computed TomographyDrug Delivery SystemsFemaleLiverPoloxamerSwineTemperatureTissue DistributionTomography, X-Ray ComputedUltrasonographyAntibiotics, AntineoplasticDoxorubicinHydrogelsPoloxamer

Identifiers

PMID39700200
PMCPMC11658602

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.