Evidence map›Paper›PMID 24452808›Full record

ArticlePharmaceutical research2014

Encapsulation of poorly soluble drugs in polymer-drug conjugates: effect of dual-drug nanoformulations on cancer therapy.

Thulani H Senanayake, Yaman Lu, Anna Bohling, Srikumar Raja, Hamid Band, Serguei V Vinogradov

Abstract read
In one paragraph

Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Drug conjugates-an emerging approach to treat breast cancer.Pharmacology research & perspectives · 2018
    Review
  6. Self-assembling prodrugs.Chemical Society reviews · 2017
    Review
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

6 authors at 2 institutions in 1 country.

Thulani H SenanayakeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, 68198-6025, USA.
Yaman Lu
Anna Bohling
Srikumar Raja
Hamid Band
Serguei V Vinogradov
Nebraska Medical Center · USUniversity of Nebraska Medical Center · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Apar Kishor Ganti · 1985 to 2026
$55.0M
TYROSINE KINASE REGULATION VIA PROTEIN DEGRADATIONR01CA087986 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2000 to 2015
$4.2M
MOLECULAR CONTROL OF EGF RECEPTOR DOWN-REGULATIONR01CA099163 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2003 to 2012
$3.7M
Targeting Endocytic Recycling of EGF Receptor in Cancer R01CA105489 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2004 to 2014
$3.0M
ErbB2 Downregulation Through HSP90 InhibitionR01CA116552 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2007 to 2011
$1.4M
Overcoming Drug Resistance to Nucleoside Analogs by Tumor-Targeted Active NanoforR01CA136921 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI VINOGRADOV, SERGUEI V · 2009 to 2013
$1.1M
NCI NIH HHS CA105489NCI NIH HHS CA116552NCI NIH HHS CA136921NCI NIH HHS CA87986NCI NIH HHS CA99163NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA087986NCI NIH HHS R01 CA099163NCI NIH HHS R01 CA105489NCI NIH HHS R01 CA116552NCI NIH HHS R01 CA136921
6 · The paper itself

Abstract

purposeCurrent cancer chemotherapy is gradually shifting to the application of drug combinations that prevent development of drug resistance. Many anticancer drugs have poor solubility and limited oral bioavailability. Using an innovative approach, we developed dual-drug nanoformulations of a polymeric nanogel conjugate with anticancer 5-FU nucleoside analog, floxuridine (FLOX), and the second anticancer drugs, paclitaxel (PCL), or a geldanamycin analog, 17-AAG, for combination therapy.

methodsPCL or 17-AAG had been encapsulated in the cholesteryl-polyvinyl alcohol-floxuridine nanogel (CPVA-FLOX) by simple solution mixing and sonication. Dual nanodrugs formed particles with diameter 180 nm and either drug content (5-20%) that were stable and could be administered orally. Their cytotoxicity in human and mouse cancer cells was determined by MTT assay, and cellular target inhibition - by Western blot analysis. Tumor growth inhibition was evaluated using an orthotopic mouse mammary 4T1 cancer model.

resultsCPVA-FLOX was more potent than free drug in cancer models including drug-resistant ones; while dual nanodrugs demonstrated a significant synergy (CPVA-FLOX/PCL), or showed no significant synergy (CPVA-FLOX/17-AAG) compared to free drugs (PCL or 17-AAG). Dual nanodrug CPVA-FLOX/17-AAG effect on its cellular target (HSP70) was similar to 17-AAG alone. In animal model, however, both dual nanodrugs effectively inhibited tumor growth compared to CPVA-FLOX after oral administration.

conclusionOral dual-drug nanoformulations of poorly-soluble drugs proved to be a highly efficient combination anticancer therapy in preclinical studies.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalChemistry, PharmaceuticalDrug CompoundingFemaleHSP70 Heat-Shock ProteinsHumansMiceMice, Inbred BALB CNanoparticlesPolymersSolubilityAntineoplastic AgentsHSP70 Heat-Shock ProteinsPolymers

Identifiers

PMID24452808
PMCPMC4038665
OpenAlexW2021933947

What OpenQuestion holds

Textmetadata
LicenceTDM
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.