Evidence map›Paper›PMID 36447020›Full record

ArticlePharmaceutical research2024

Optimization of Lung Surfactant Coating of siRNA Polyplexes for Pulmonary Delivery.

Domizia Baldassi, Thi My Hanh Ngo, Olivia M Merkel

Open access · hybridAbstract read
In one paragraph

Article in Pharmaceutical research, 2024. 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
0.9field-weighted citation impact, top 28% 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, 10 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 1 institution in 1 country.

Domizia BaldassiDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians University of Munich, Butenandtstraße 5, 81377, Munich, Germany.
Thi My Hanh NgoDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians University of Munich, Butenandtstraße 5, 81377, Munich, Germany.
Olivia M MerkelDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians University of Munich, Butenandtstraße 5, 81377, Munich, Germany. olivia.merkel@lmu.de.ORCID http://orcid.org/0000-0002-4151-3916
Ludwig-Maximilians-Universität München · DE

Funding

H2020 Excellent Science ERC-2014-StG - 637830
6 · The paper itself

Abstract

purposeThe aim of this study was to understand how coating with a pulmonary surfactant, namely Alveofact, affects the physicochemical parameters as well as in vitro behavior of polyethylenimine (PEI) polyplexes for pulmonary siRNA delivery.

methodsAlveofact-coated polyplexes were prepared at different Alveofact:PEI coating ratios and analyzed in terms of size, PDI and zeta potential as well as morphology by transmission electron microscopy. The biological behavior was evaluated in a lung epithelial cell line regarding cell viability, cellular uptake via flow cytometry and gene downregulation by qRT-PCR. Furthermore, a 3D ALI culture model was established to test the mucus diffusion and cellular uptake by confocal microscopy as well as gene silencing activity by qRT-PCR.

resultsAfter optimizing the coating process by testing different Alveofact:PEI coating ratios, a formulation with suitable parameters for lung delivery was obtained. In lung epithelial cells, Alveofact-coated polyplexes were well tolerated and internalized. Furthermore, the coating improved the siRNA-mediated gene silencing efficiency. Alveofact-coated polyplexes were then tested on a 3D air-liquid interface (ALI) culture model that, by expressing tight junctions and secreting mucus, resembles important traits of the lung epithelium. Here, we identified the optimal Alveofact:PEI coating ratio to achieve diffusion through the mucus layer while retaining gene silencing activity. Interestingly, the latter underlined the importance of establishing appropriate in vitro models to achieve more consistent results that better predict the in vivo activity.

conclusionThe addition of a coating with pulmonary surfactant to polymeric cationic polyplexes represents a valuable formulation strategy to improve local delivery of siRNA to the lungs.

Indexed as

Pulmonary SurfactantsLungPolyethyleneimineRNA, Small InterferingSurface-Active AgentsPolyethyleneiminePulmonary SurfactantsRNA, Small InterferingSurface-Active Agentsair-liquid interfacepolyplexespulmonary deliverypulmonary surfactantsiRNA delivery

Identifiers

PMID36447020
PMCPMC9708138
OpenAlexW4310458961

What OpenQuestion holds

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Registered trials

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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.