Evidence map›Paper›PMID 31068126›Full record

ArticleBMC neuroscience2019

In vitro characterization of odorranalectin for peptide-based drug delivery across the blood-brain barrier.

Ravi K Sajja, Predrag Cudic, Luca Cucullo

Open access · goldAbstract read
In one paragraph

Article in BMC neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

7 citing papers in PubMed, 9 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

3 authors at 2 institutions in 1 country.

Ravi K SajjaDepartment of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX, 79106, USA.
Predrag CudicDepartment of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL, USA.
Luca CuculloDepartment of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX, 79106, USA. luca.cucullo@ttuhsc.edu.ORCID 0000-0002-2827-7162
Texas Tech University · USFlorida Atlantic University · US

Funding

Testing tobacco smoke toxicity at the blood-brain barrierR01DA029121 · NIDA · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI ABBRUSCATO, THOMAS J, CUCULLO, LUCA · 2011 to 2021
$3.6M
Blood and Brain Based Biomarkers of Injury to Assess the Cerebrovascular Impact of Emerging Alternatives to Classic Cigarette ProductsR01DA049737 · NIDA · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI ABBRUSCATO, THOMAS J, CUCULLO, LUCA · 2019 to 2021
$1.4M
Novel opioid peptides for nose to brain deliveryR21DA039722 · NIDA · FLORIDA ATLANTIC UNIVERSITY · PI CUDIC, PREDRAG · 2016 to 2017
$455k
NIDA NIH HHS R01 DA029121NIDA NIH HHS R21 DA039722
6 · The paper itself

Abstract

backgroundThe use of siRNA-based gene silencing has been recently underscored as a potential therapeutic strategy for the treatment of neurological disorders. However, the stability of siRNA and other small molecule therapeutics is challenged by their intrinsic instability and limited passage across the blood-brain barrier (BBB). Based on these premises, our objective was to characterize/optimize odorranalectin (OL), a small non-immunogenic lectin-like peptide, as a carrier for targeted delivery across the BBB. For this purpose, 5(6)-carboxyfluorescein-conjugated OL and scramble peptide were synthesized, and then their BBB cellular internalization/trafficking and stability were characterized versus temperature, pH and serum content in the media in hCMEC/D3 cells as a model of BBB endothelium. Specifically, integrity of the internalized peptide in cell lysates was analyzed by LC/MS while cellular distribution and intracellular trafficking of OL was examined by fluorescence microscopy with early-late endosome (pHRodo Red

resultsOur data show that cellular uptake of OL increased linearly with the concentrations tested in this study at 37 °C and the uptake was two to threefolds higher when compared to scramble peptide. While there were no differences for scramble peptide, the uptake of OL decreased by 50% at 4 °C incubation (vs. 37 °C). No effects of pH were observed on endothelial uptake of OL. Immunofluorescence studies also indicated a significant cellular internalization of OL that remained intact (as evaluated by LC-MS/MS) and co-localized with endosomal, but not lysosome marker. Importantly, OL was found non-toxic to cells at all concentrations tested.

conclusionsIn summary, our data suggest the existence of a receptor-mediated transcytosis pathway for cellular uptake of OL at the BBB endothelium. However, in vivo studies will be needed to assess the siRNA loading capacity of OL and its trans-BBB transport efficiency for targeted delivery in the brain.

Indexed as

Blood-Brain BarrierCells, CulturedCell SurvivalDose-Response Relationship, DrugDrug Delivery SystemsDrug StabilityEndosomesFluoresceinsHumansLectinsLysosomes6-carboxyfluoresceinFluoresceinsLectinsodorranalectin, Odorrana grahamiBBBCNS disordersCyclic peptidehCMEC/D3siRNA delivery

Identifiers

PMID31068126
PMCPMC6505199
OpenAlexW2947334208

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.