# Nanocarriers Derived from Annona squamosa Seed Oil Amplify the Anti-inflammatory Effect of Carvacrol in Human Neutrophils

**Authors:** Sarah Brenda Ferreira dos Santos, Stéfano Arrais Pereira, Maria Júlia Pereira dos Santos, Louhana Moreira Rebouças, Francisco Alessandro Marinho Rodrigues, João Francisco Câmara Neto, Matheus da Silva Campelo, Luzia Kalyne Almeida Moreira Leal, Francisca Rayssa Mesquita, Denise Ramos Moreira, Victor Borges Fernandes, Ícaro Gusmão Pinto Vieira, Nágila Maria Pontes Silva Ricardo

PMC · DOI: 10.1021/acsomega.5c12743 · 2026-02-17

## TL;DR

Researchers developed nanoemulsions from Annona squamosa seed oil to deliver carvacrol, which reduced inflammation in human neutrophils more effectively than free carvacrol.

## Contribution

The study introduces a novel nanoemulsion system using Annona squamosa seed oil to enhance carvacrol's anti-inflammatory effects in neutrophils.

## Key findings

- Nanoemulsions showed colloidal stability with particle sizes around 170 nm and high encapsulation efficiency (>99%).
- Carvacrol-loaded nanoemulsions reduced neutrophil degranulation at lower concentrations than free carvacrol.
- The Korsmeyer–Peppas model best described the prolonged carvacrol release from the nanoemulsions.

## Abstract

This research aimed to prepare nanoemulsions based on Annona squamosa seed oil (ASSO) for encapsulation
of carvacrol (CARV) and subsequent evaluation of its cytotoxicity
and anti-inflammatory potential in human neutrophils. The chemical
composition of ASSO is rich in long-chain fatty acids, especially
oleic and linoleic acids. The treatment of human neutrophils with
ASSO demonstrated its low cytotoxicity (1–50 μg mL–1), as well as anti-inflammatory effect at 25 and 50
μg mL–1, being able to attenuate the release
of myeloperoxidase (MPO). The nanocarriers presented colloidal stability
with particle sizes around 170 nm, ζ-potential greater than
|30 mV| and moderate polydispersity. The encapsulation efficiency
of the nanosystems was greater than 99%, evidencing the effectiveness
of the applied methodology for CARV entrapment. The drug release tests
demonstrated that the nanoemulsions were able to prolong the carvacrol
release process, with an accumulated release of 26% (745 μg)
in 72 h, with the Korsmeyer–Peppas model being the one that
best adjusted to the observed kinetics. CARV, carvacrol-loaded nanoemulsion
(CNE), and blank nanoemulsion (BNE) showed low cytotoxicity (5–100
μg mL–1) against human neutrophils and were
able to reduce neutrophil degranulation. Notably, the CNE potentiated
the anti-inflammatory effect of the CARV, demonstrating biological
efficacy at lower concentrations (5 μg mL–1) compared to the free drug (50 μg mL–1).
Thus, nanoemulsions based on ASSO were effectively enhanced the biological
effects of CARV, positioning themselves as promising nanosystems for
the encapsulation and delivery of lipophilic compounds.

## Linked entities

- **Proteins:** MPO (myeloperoxidase)
- **Chemicals:** carvacrol (PubChem CID 10364), oleic acid (PubChem CID 445639), linoleic acid (PubChem CID 5280450)
- **Species:** Annona squamosa (taxon 301693), Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MPO (myeloperoxidase) [NCBI Gene 4353], PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ISYNA1 (inositol-3-phosphate synthase 1) [NCBI Gene 51477] {aka INO1, INOS, IPS, IPS 1, IPS-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** psoriasis (MESH:D011565), systemic lupus erythematosus (MESH:D008180), inflammatory bowel disease (MESH:D015212), autoimmune conditions (MESH:D001327), inflammatory drug (MESH:D000081015), immune-mediated diseases (MESH:C567355), cancer (MESH:D009369), renal, gastrointestinal and cardiovascular toxicity (MESH:D005767), cardiovascular disorders (MESH:D002318), Cytotoxicity (MESH:D064420), rheumatoid arthritis (MESH:D001172), chronic inflammation (MESH:D007249), Sink Conditions (MESH:D020763), liver diseases (MESH:D008107), anemia (MESH:D000740), cardiopathies (MESH:C536187)
- **Chemicals:** hydrogen (MESH:D006859), DAG (MESH:D004075), copper (MESH:D003300), PBS (MESH:D007854), poly(propylene oxide) (MESH:C012504), argon (MESH:D001128), reactive oxygen species (MESH:D017382), H2SO4 (MESH:C033158), vegetable oil (MESH:D010938), DMSO (MESH:D004121), EE (MESH:D004997), EtOH (MESH:D000431), steroids (MESH:D013256), water (MESH:D014867), prostaglandin E2 (MESH:D015232), essential oil (MESH:D009822), chloroform (MESH:D002725), Indo (MESH:D007213), PMA (MESH:D013755), poly(ethylene oxide) (MESH:D011092), Na2SO4 (MESH:C012036), Fatty Acids (MESH:D005227), Oil (MESH:D009821), polymer (MESH:D011108), carbon (MESH:D002244), hypochlorous acid (MESH:D006997), Triton X-100 (MESH:D017830), Acetonitrile (MESH:C032159), triacylglycerol (MESH:D014280), ester (MESH:D004952), linoleic acids (MESH:D008041), He (MESH:D006371), 5-isopropyl-2-methylphenol (MESH:C073316), Trypan Blue (MESH:D014343), H2O2 (MESH:D006861), 3,3',3,5'-tetramethylbenzidine (-), Pluronic F127 (MESH:D020442), phosphate (MESH:D010710), sodium citrate (MESH:D000077559), acids (MESH:D000143), unsaturated fatty acids (MESH:D005231), hexane (MESH:D006586), Nile red (MESH:C044808)
- **Species:** Homo sapiens (human, species) [taxon 9606], Annona squamosa (sugar-apple, species) [taxon 301693], A. squamosa [taxon 500147]

## Figures

15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961537/full.md

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Source: https://tomesphere.com/paper/PMC12961537