Evidence map›Paper›PMID 37754854›Full record

ArticleJournal of functional biomaterials2023

Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders.

Maria Del Moral, Maximilian Loeck, Eameema Muntimadugu, Guillem Vives, Vy Pham, Peter Pfeifer, Giuseppe Battaglia, Silvia Muro

Open access · goldAbstract read
In one paragraph

Article in Journal of functional biomaterials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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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

8 authors at 4 institutions in 2 countries.

Maria Del MoralInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.
Maximilian LoeckInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.
Eameema MuntimaduguInstitute for Bioscience and Biotechnology Research (IBBR), University of Maryland, College Park, MD 20742, USA.ORCID 0000-0001-6942-2189
Guillem VivesInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.
Vy PhamInstitute for Bioscience and Biotechnology Research (IBBR), University of Maryland, College Park, MD 20742, USA.
Peter PfeiferInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.
Giuseppe BattagliaInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.ORCID 0000-0003-3349-6770
Silvia MuroInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain.ORCID 0000-0003-1900-352X
Barcelona Institute of Science and Technology · ESInstitució Catalana de Recerca i Estudis Avançats · ESUniversity of Maryland, College Park · USUniversitat Autònoma de Barcelona · ES

Funding

Targeted replacement of defective lysosomal enzymes in the lung and brainR01HL098416 · NHLBI · UNIV OF MARYLAND, COLLEGE PARK · PI MURO, SILVIA · 2010 to 2020
$3.3M
NHLBI NIH HHS R01 HL098416NIH HHS R01-HL98416
6 · The paper itself

Abstract

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤-35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56-78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs.

Indexed as

copolymer ratioenzyme releaseenzyme replacement therapyhyaluronidaselysosomal storage disordernanoparticle stabilitypoly(lactide-co-glycolide) nanoparticles

Identifiers

PMID37754854
PMCPMC10531859
OpenAlexW4386169059

What OpenQuestion holds

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LicenceCC BY
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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.