Evidence map›Paper›PMID 40438965›Full record

ReviewTherapeutic delivery2025

The role of excipients in lipid nanoparticle metabolism: implications for enhanced therapeutic effect.

Karlene L M Knaggs, Yikai Sun, Brianna A Walz, Janice Pang, Omar F Khan

Abstract readReview
In one paragraph

Review in Therapeutic delivery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

5 authors.

Karlene L M KnaggsInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Yikai SunInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Brianna A WalzInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Janice PangInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Omar F KhanInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are multicomponent delivery vehicles for nucleic acids that are generally comprised of ionizable lipids, phospholipids, cholesterol and lipid-poly(ethylene glycol) molecules. It is well established that both the composition and relative amounts of each component significantly impact the efficiency of nucleic acid delivery by LNPs, as well as their organ-specific targeting. However, the post-delivery fate of every component is less discussed such as the degradation, clearance, and retention in the body. The longevity and metabolites of each component can greatly influence overall tolerability and safety. For instance, slowly degrading ionizable lipids, which comprise around 50% of the LNP, have been shown to illicit an extended inflammatory response. In this review significant importance is placed on chemistries that improve the tolerability and safety of certain LNP components, such as molecular modifications to ionizable lipids, lipid-poly(ethylene glycol) and nucleic acids. Additionally, we discuss how formulation strategies, such as the amount of cholesterol and phospholipids added to optimize clearance, can enhance biodegradability and reduce inflammation. Furthermore, this review will provide an understanding of the considerations around designing LNP components for better or more predictable metabolism such modified nucleic acids and biodegradable chemical linkers in ionizable lipids.

Indexed as

ExcipientsLipidsNanoparticlesNucleic AcidsAnimalsDrug Delivery SystemsHumansPhospholipidsPolyethylene GlycolsExcipientsLipidsNucleic AcidsPhospholipidsPolyethylene GlycolsClearancedegradationexcipientsionizable lipidslipid-nanoparticlesmetabolismmetabolitesRNA therapeutics

Identifiers

PMID40438965
PMCPMC12218425

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.