Evidence map›Paper›PMID 34777605›Full record

ArticleCellular and molecular bioengineering2021

Crystallization of the Multi-Receptor Tyrosine Kinase Inhibitor Sorafenib for Controlled Long-Term Drug Delivery Following a Single Injection.

Victoria Lai, Sarah Y Neshat, Amanda Rakoski, James Pitingolo, Johndavid Sabedra, Stephen Li, Aryaman Shodhan, Joshua C Doloff

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular bioengineering, 2021. 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
0.2field-weighted citation impact, top 46% of its field
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 citations in OpenAlex.

  1. Intraocular delivery of crystalline sorafenib provides sustained, potent inhibition of wet age-related macular degeneration.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Victoria Lai *Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
Sarah Y Neshat *Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
Amanda RakoskiDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
James PitingoloDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
Johndavid SabedraDepartment of Materials Science and Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218 USA.
Stephen LiDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
Aryaman ShodhanDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.
Joshua C DoloffDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute/Smith Bldg., Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21287 USA.ORCID 0000-0002-4323-3264
Johns Hopkins University · USBloomberg (United States) · US

Funding

BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
NIGMS NIH HHS T32 GM007057
6 · The paper itself

Abstract

introductionA major challenge in cancer medicine is the safe and effective delivery of drugs to the right tissue at the right time. Despite being designed for greater target specificity, many drugs still result in side effects and lack of safety in patients following global dissemination. Therefore, to develop new, more effective formulations capable of improving specificity and reducing off-target effects, here we describe formulation of drug crystals, from even a very hydrophobic and otherwise difficult to solubilize small molecule chemical compound, capable of providing constant drug release for weeks following a single injection.

methodsWe chose to utilize the multi-tyrosine kinase inhibitor and multi-modal (anti-angiogenic and tumor cell cytotoxic) agent sorafenib, to combat aberrant angiogenesis and tumor growth which contribute to metastasis, ultimately responsible for poor patient outcomes. We tuned crystal size (surface area:volume ratios), imaged by SEM, to display controllability of drug delivery kinetics in

resultsSingle and powder crystal X-ray diffraction (XRD) established that all crystals were the same polymorph and drug form. When utilized against an orthotopic triple negative breast cancer (TNBC) mouse model (4T1 in syngeneic BALB/c mice), we established anti-tumor activity from a single local, subcutaneous injection of crystalline sorafenib.

conclusionFrom our findings, we support that engineering crystalline drug delivery systems has implications in the treatment of cancer or other diseases where high enough constitutive drug levels are needed to maintain target saturation and inhibition while also preventing emergence of drug resistance, which is a consequence often seen with suboptimal dosing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00708-6.

Indexed as

Anti-angiogenesisBreast cancerControlled releaseCrystallizationDrug crystalsDrug delivery

Identifiers

PMID34777605
PMCPMC8548453
OpenAlexW3205914202

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.