Evidence map›Paper›PMID 41074180›Full record

ArticleJournal of nanobiotechnology2025

A novel scalable method for the production of rennet-treated milk-derived extracellular vesicles for improved curcumin oral delivery.

Emily Schifano, Francesco Vari, Luca Buccini, Mariana Karimova, Kuanysh Syman, Diana Varnadyan, Daniela Uccelletti, Simone Dinarelli, Maurizio Zuccotti, Andrea Alfieri and 5 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2025. 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
–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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Interplay of Interleukin-1Oncology research · 2026
    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

15 authors.

Emily Schifano *Department of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy.
Francesco Vari *Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Luca Buccini *Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy.
Mariana KarimovaDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy.
Kuanysh SymanDepartment of Biology Faculty of Natural Science and Geography, Abai KazakhNational Pedagogical University Almaty, Almaty, Kazakhstan.
Diana VarnadyanDepartment of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
Daniela UccellettiDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy.
Simone DinarelliInstitute for the Structure of Matter, National Research Council, Roma, Italy.
Maurizio ZuccottiDepartment of Biology and Biotechnology "Lazzaro Spallanzani', University of Pavia, Pavia, Italy.
Andrea AlfieriCentro Grandi Strumenti, University of Pavia, Pavia, Italy.
Simona SennatoInstitute for Complex Systems (ISC)-CNR and Physics Department, Sapienza University, Rome, Italy.
Francesco MuraResearch Center of Nanotechnologies for Engineering (CNIS), Sapienza University of Rome, Rome, Italy.
Marco RossiDepartment of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy.
Luciana DiniDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy. luciana.dini@uniroma1.it.
Stefano TacconiDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy. stefano.tacconi@uniroma1.it.

Funding

RICERCA_SAPIENZA_2022_GRANDI RG1221816C3E1A69RICERCA_SAPIENZA_2023_MEDI RM123188F780655
6 · The paper itself

Abstract

backgroundExtracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles secreted by all cell types and are gaining increasing attention as natural, biocompatible drug delivery nanovehicles. Among the various sources, bovine milk-derived EVs (MEVs) represent an abundant, cost-effective, and eco-friendly alternative, with demonstrated potential in delivering chemotherapeutics, bioactive natural compounds, miRNAs, and other therapeutic agents. However, the effective and scalable production of MEVs still requires protocol optimization for contaminant removal, especially casein micelles and fat globules, which may be co-isolated and compromise EV quality. This study aimed to identify an efficient and scalable strategy for MEV production suitable for oral drug delivery applications.

resultsThree casein removal methods, acetic acid precipitation, ultracentrifugation, and commercial rennet, each combined with ultrafiltration/size exclusion chromatography (UF/SEC) for EV isolation were compared. Rennet treatment outperformed the other methods, yielding MEVs with superior purity, integrity, and minimal aggregation. MEVs with high quality and purity from whey derived from rennet-treated bovine milk successfully isolated by tangential flow filtration (TFF), a method more suitable for large-scale production. These vesicles were subsequently employed for the passive loading of curcumin, a hydrophobic compound with known bioactive properties but poor intrinsic bioavailability. The resulting curcumin-loaded MEVs (CurMEVs) were evaluated for their ability to traverse the intestinal barrier using in vitro and in vivo models. In addition, a prolongevity effect was observed in Caenorhabditis elegans animals supplemented with CurMEVs. Results confirmed that MEVs enhance curcumin stability and bioavailability.

conclusionsOur findings support the use of rennet combined with SEC or TFF to produce MEVs as scalable, safe, and effective delivery systems, offering a promising platform for future nutraceutical and pharmaceutical applications. In parallel, the study highlights the added value of converting dairy industry by-products, such as whey, into a sustainable source of nanocarriers.

Indexed as

CurcuminDrug Delivery SystemsExtracellular VesiclesMilkAdministration, OralAnimalsBiological AvailabilityCaseinsCattleDrug CarriersHumansNanoparticlesCaseinsCurcuminDrug Carriers

Identifiers

PMID41074180
PMCPMC12514809

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.