Evidence map›Paper›PMID 34114163›Full record

ArticlePharmaceutical research2021

Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose.

Farrokh Sharifi, Yazan J Meqbil, Andrew Otte, Anna M Gutridge, Arryn T Blaine, Richard M van Rijn, Kinam Park

Open access · bronzeAbstract read
In one paragraph

Article in Pharmaceutical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 53% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. 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

7 authors at 1 institution in 1 country.

Farrokh SharifiPurdue University, Weldon School of Biomedical Engineering, West Lafayette, Indiana, 47907, USA.
Yazan J MeqbilPurdue University, Department of Medicinal Chemistry and Molecular Pharmacology, West Lafayette, Indiana, 47907, USA.
Andrew OttePurdue University, Weldon School of Biomedical Engineering, West Lafayette, Indiana, 47907, USA.
Anna M GutridgePurdue University, Department of Medicinal Chemistry and Molecular Pharmacology, West Lafayette, Indiana, 47907, USA.
Arryn T BlainePurdue University, Department of Medicinal Chemistry and Molecular Pharmacology, West Lafayette, Indiana, 47907, USA.
Richard M van RijnPurdue University, Department of Medicinal Chemistry and Molecular Pharmacology, West Lafayette, Indiana, 47907, USA.
Kinam ParkPurdue University, Weldon School of Biomedical Engineering, West Lafayette, Indiana, 47907, USA. kpark@purdue.edu.ORCID http://orcid.org/0000-0001-8202-6084
Purdue University West Lafayette · US

Funding

Injectable naltrexone 2-month depot formulationsUH3DA048774 · NIDA · PURDUE UNIVERSITY · PI PARK, KINAM · 2022 to 2024
$4.9M
Injectable naltrexone 2-month depot formulationsUG3DA048774 · NIDA · PURDUE UNIVERSITY · PI PARK, KINAM · 2019 to 2020
$2.9M
G-protein-, beta-arrestin- and ERK-signaling in alcohol use- and anxiety-disordersR01AA025368 · NIAAA · PURDUE UNIVERSITY · PI CHESTER, JULIA ANN · 2017 to 2021
$1.7M
NIAAA NIH HHS AA025368NIAAA NIH HHS R01 AA025368NIDA NIH HHS UG3 DA048774NIDA NIH HHS UH3 DA048774Ralph W. and Grace M. Showalter Research Trust Fund 2020-KP
6 · The paper itself

Abstract

purposeOpioids have been the main factor for drug overdose deaths in the United States. Current naloxone delivery systems are effective in mitigating the opioid effects only for hours. Naloxone-loaded poly(lactide-co-glycolide) (PLGA) microparticles were prepared as quick- and long-acting naloxone delivery systems to extend the naloxone effect as an opioid antidote.

methodsThe naloxone-PLGA microparticles were made using an emulsification solvent extraction approach with different formulation and processing parameters. Two PLGA polymers with the lactide:glycolide (L:G) ratios of 50:50 and 75:25 were used, and the drug loading was varied from 21% to 51%. Two different microparticles of different sizes with the average diameters of 23 μm and 50 μm were produced using two homogenization-sieving conditions. All the microparticles were critically characterized, and three of them were evaluated with β-arrestin recruitment assays.

resultsThe naloxone encapsulation efficiency (EE) was in the range of 70-85%. The EE was enhanced when the theoretical naloxone loading was increased from 30% to 60%, the L:G ratio was changed from 50:50 to 75:25, and the average size of the particles was reduced from 50 μm to 23 μm. The in vitro naloxone release duration ranged from 4 to 35 days. Reducing the average size of the microparticles from 50 μm to 23 μm helped eliminate the lag phase and obtain the steady-state drug release profile. The cellular pharmacodynamics of three selected formulations were evaluated by applying DAMGO, a synthetic opioid peptide agonist to a μ-opioid receptor, to recruit β-arrestin 2.

conclusionsNaloxone released from the three selected formulations could inhibit DAMGO-induced β-arrestin 2 recruitment. This indicates that the proposed naloxone delivery system is adequate for opioid reversal during the naloxone release duration.

Indexed as

AnimalsCHO CellsCricetulusDelayed-Action PreparationsDrug CarriersDrug LiberationHumansMicrospheresNaloxoneNarcotic AntagonistsOpiate OverdoseParticle SizePolylactic Acid-Polyglycolic Acid CopolymerSurface PropertiesTime FactorsDelayed-Action PreparationsDrug CarriersNaloxoneNarcotic AntagonistsPolylactic Acid-Polyglycolic Acid CopolymerDAMGOdrug loadingencapsulation efficiencynaloxoneopioid overdosePLGA microparticleszero-order releaseβ-arrestin 2 inhibition

Identifiers

PMID34114163
PMCPMC8192039
OpenAlexW3168216624

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.