Evidence map›Paper›PMID 31415878›Full record

ArticleInternational journal of pharmaceutics2019

A solid lipid nanoparticle formulation of 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine with increased solubility, stability, and antitumor activity.

Solange A Valdes, Riyad F Alzhrani, Andres Rodriguez, Dharmika S P Lansakara-P, Sachin G Thakkar, Zhengrong Cui

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

Article in International journal of pharmaceutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 32 citations in OpenAlex.

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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 2 countries.

Solange A ValdesDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, United States.
Riyad F AlzhraniDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, United States.
Andres RodriguezAdvanced Center for Chronic Diseases, Santiago, Chile.
Dharmika S P Lansakara-PDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, United States.
Sachin G ThakkarDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, United States.
Zhengrong CuiDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, United States. Electronic address: zhengrong.cui@austin.utexas.edu.
The University of Texas at Austin · USAdvanced Center for Chronic Diseases · CL

Funding

Overcoming pancreatic tumor resistance to gemcitabineR01CA135274 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI CUI, ZHENGRONG · 2008 to 2017
$2.8M
A Creative Integration of Omega-3 Fatty Acids into Pancreatic Cancer ChemotherapyR21CA179362 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI CUI, ZHENGRONG · 2015 to 2016
$371k
NCI NIH HHS R01 CA135274NCI NIH HHS R21 CA179362
6 · The paper itself

Abstract

Previously, we synthesized 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), a novel lipophilic compound with a potent, broad-spectrum antitumor activity. Herein, we report a solid lipid nanoparticle (SLN) formulation of DHA-dFdC with improved apparent aqueous solubility, chemical stability, as well as efficacy in a mouse model. The SLNs were prepared from lecithin/glycerol monostearate-in-water emulsions emulsified with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Tween 20. The resultant DHA-dFdC-SLNs were 102.2 ± 7.3 nm in diameter and increased the apparent solubility of DHA-dFdC in water to at least 5.2 mg/mL, more than 200-fold higher than its intrinsic water solubility. DHA-dFdC in a lyophilized powder of DHA-dFdC-SLNs was significantly more stable than the waxy solid of pure DHA-dFdC. DHA-dFdC-SLNs also showed an increased cytotoxicity against certain tumor cells than DHA-dFdC. The plasma concentration of DHA-dFdC in mice intravenously injected with DHA-dFdC-SLNs in dispersion followed a bi-exponential model, with a half-life of ~44 h. In mice bearing B16-F10 murine melanoma, DHA-dFdC-SLNs were significantly more effective than DHA-dFdC in controlling the tumor growth. In addition, histology evaluation revealed a high level of apoptosis and tumor encapsulation in tumors in mice treated with DHA-dFdC-SLNs. DHA-dFdC-SLNs represents a new DHA-dFdC formulation with improved antitumor activity.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorDeoxycytidineDrug CarriersDrug Delivery SystemsEmulsionsFemaleLecithinsLipidsMiceMice, Inbred C57BLNanoparticlesParticle SizePolyethylene GlycolsSolubilityAntineoplastic AgentsDeoxycytidineDrug CarriersEmulsionsLecithinsLipidspolyethylene glycol 1000Polyethylene GlycolsVitamin EAntitumor activityCytotoxicityPlasma pharmacokineticsSolid lipid nanoparticlesSolubilityStability

Identifiers

PMID31415878
PMCPMC6824728
OpenAlexW2967455311

What Socratic 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 Socratic graph.