# Casimiroa edulis Leaf Extract–Loaded PLGA Nanoparticles: Untargeted Phytochemical Profiling and Wound-Healing-Oriented Antioxidant/Occlusive Characterization

**Authors:** Clara Luisa Domínguez-Delgado, Mariana Montserrat Guadarrama-López, Yair Cruz-Narváez, Rafael Iván Puente-Lee, Sergio Arturo Ojeda-Piedra, María de la Luz Zambrano-Zaragoza

PMC · DOI: 10.3390/pharmaceutics18020249 · 2026-02-17

## TL;DR

Researchers developed biodegradable nanoparticles loaded with Casimiroa edulis leaf extract, which showed promising antioxidant properties for wound healing.

## Contribution

The first characterization of Casimiroa edulis leaf extract-loaded nanoparticles for wound healing with phytochemical profiling and antioxidant/occlusive evaluation.

## Key findings

- Casimiroa edulis leaf extract contains polyphenols like tetramethylscutellarein and rutin, identified via mass spectrometry.
- Nanoparticles with an average size of 169.30 nm and 57% encapsulation efficiency were successfully produced.
- The extract-loaded nanoparticles showed higher antioxidant activity than previously reported for sapote seeds.

## Abstract

Background: Nanoparticles are a promise for wound-healing therapies. However, its lack of efficacy/safety represents a real challenge for therapeutic use. Objectives: To overcome these problems, the ethanolic extract of Casimiroa edulis leaves, previously reported for its anti-inflammatory, antibiotic, and antioxidant activities, was characterized by FIA-ESI-FTICR-MS and encapsulated in biodegradable nanoparticles for potential wound-healing therapies. Methods:
Casimiroa edulis-loaded nanoparticles (CE-NP) were prepared using the rapid emulsion-diffusion method and characterized by their particle size distribution, molecular interactions, charge, morphology, pH, physical stability, and antioxidant and occlusive effects. Results: A total of 40/34 ions in positive/negative electrospray ionization modes were obtained from the extract exploration analysis and were putatively annotated by accurate mass against databases with an error tolerance ≤10 mDa. The most abundant compounds showed the following order: tetramethylscutellarein > rutin > S-usnate > lactose > eugenol derivative > rotenone. While polyphenols predominated, carbohydrates, depsidones/other phenolics, etc., were also detected. The solid/spherical nanoparticles observed by TEM were obtained with a blend of acetone:methyl ethyl ketone (75:25) as the organic phase, producing a unimodal particle size (169.30 ± 1.30 nm; PdI = 0.08 ± 0.03). The encapsulation/loading percentages were 57 ± 0.74/1.62 ± 0.02%, ensuring an entrapment of half the extract, as observed in the FTIR studies. The light backscatter profiles show minimal differences, indicating physical stability correlated with the Z potential (−9.45 ± 1.73 mV). The antioxidant activity of the extract/nanoparticles at 40 µg/mL was 17.27 ± 2.86/16.73 ± 1.28 μg/mL, two-fold higher than that previously reported for sapote seeds. Conclusions: Biodegradable CE-NP with suitable characteristics were obtained for the first time, representing a preliminary proposal for wound healing. Efficacy studies are required.

## Linked entities

- **Chemicals:** tetramethylscutellarein (PubChem CID 96118), rutin (PubChem CID 5280805), S-usnate (PubChem CID 25202099), lactose (PubChem CID 6134), rotenone (PubChem CID 6758)
- **Species:** Casimiroa edulis (taxon 68535)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, ARG1 (arginase 1) [NCBI Gene 383], COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, CAT (catalase) [NCBI Gene 847], MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, Esr1 (estrogen receptor 1 (alpha)) [NCBI Gene 13982] {aka ER, ER-alpha, ERa, ERalpha, ESR, Estr}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}
- **Diseases:** Diabetes (MESH:D003920), water loss (MESH:D000069578), cancer (MESH:D009369), Alzheimer's disease (MESH:D000544), ocular irritation (MESH:D001523), CE-NP (MESH:C536761), prostate cancer (MESH:D011471), melanoma (MESH:D008545), dry wound (MESH:D014947), cardiovascular and neurodegenerative disorders (MESH:D019636), inflammation (MESH:D007249), uremia (MESH:D014511), skin (MESH:D012871), pain (MESH:D010146), psoriasis (MESH:D011565), metabolic disorders (MESH:D008659), hemolysis (MESH:D006461), contracture (MESH:D003286), burn (MESH:D002056), obesity (MESH:D009765), microbial infection (MESH:D015163), stroke (MESH:D020521), dermatitis (MESH:D003872), myocardial infarction (MESH:D009203), infection (MESH:D007239), blood coagulation (MESH:D001778), cytotoxicity (MESH:D064420), rheumatoid arthritis (MESH:D001172), hypertrophic scars (MESH:D017439), colon cancer (MESH:D015179), atherosclerosis (MESH:D050197), acne (MESH:D000152), necrosis (MESH:D009336), amnesic (MESH:D000647), hepatoma (MESH:D006528), breast, prostate, lung, oral squamous cell, gastric, osteosarcoma, and cervical cancers (MESH:D018307), chronic (MESH:D002908), AGE (OMIM:613784), cataracts (MESH:D002386)
- **Chemicals:** PEG (MESH:D011092), quercetin (MESH:D011794), MDA (MESH:D015104), N (MESH:D009584), polysaccharides (MESH:D011134), norfloxacin (MESH:D009643), Lactose (MESH:D007785), C (MESH:D002244), Rutin (MESH:D012431), polymer (MESH:D011108), ester (MESH:D004952), 1, 1-diphenyl-2-picrylhydrazyl (MESH:C004931), Stilbenoids (MESH:D013267), PVA (MESH:C063253), chlorophyll (MESH:D002734), methanol (MESH:D000432), singlet-oxygen (MESH:D026082), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (MESH:C010643), withanolides (MESH:D054358), glycolic acid (MESH:C031149), caffeic acid phenethyl ester (MESH:C055494), Coniferin (MESH:C016316), Zn (MESH:D015032), oxygen (MESH:D010100), Protoporphyrin IX (MESH:C028025), n-hexane (MESH:C026385), Vicenin-2 (MESH:C530449), sugar (MESH:D000073893), chitosan (MESH:D048271), gentamicin (MESH:D005839), Cu (MESH:D003300), isothiocyanates (MESH:D017879), ascorbic acid (MESH:D001205), Alkaloids (MESH:D000470), glucosinolates (MESH:D005961), Hydrochloric acid (MESH:D006851), germanium (MESH:D005857), carboxymethyl-lysine (MESH:C048496), phenylethylamine (MESH:D010627), 2-tridecanone (MESH:C009541), silver (MESH:D012834), CE (MESH:D002563), sodium hydroxide (MESH:D012972), acetyleugenol (MESH:C081939), Ethanol (MESH:D000431), carotenoids (MESH:D002338), free radical (MESH:D005609), methyl ethyl ketone (MESH:C005222), kaempferol (MESH:C006552), aspirin (MESH:D001241), zinc oxide (MESH:D015034), Water (MESH:D014867), AGEs (MESH:D017127), imidazole (MESH:C029899), essential oil (MESH:D009822), retinol (MESH:D014801), fullerene C60 (MESH:C069837), PGE2 (MESH:D015232), Terpenes (MESH:D013729), nucleotides (MESH:D009711)
- **Species:** Clavispora lusitaniae (species) [taxon 36911], Mus musculus (house mouse, species) [taxon 10090], Nakaseomyces glabratus (species) [taxon 5478], Pseudomonas aeruginosa (species) [taxon 287], Lycium barbarum (Duke of Argyll's teatree, species) [taxon 112863], Candida albicans (species) [taxon 5476], Pichia kudriavzevii (species) [taxon 4909], Escherichia coli (E. coli, species) [taxon 562], Candida tropicalis (species) [taxon 5482], Bordetella bronchiseptica (species) [taxon 518], Salmonella enterica subsp. enterica serovar Typhimurium (no rank) [taxon 90371], Enterococcus faecalis (species) [taxon 1351], Salmonella enterica (species) [taxon 28901], Shigella sonnei (species) [taxon 624], Casimiroa edulis (matasano, species) [taxon 68535], Rattus norvegicus (brown rat, species) [taxon 10116], Vibrio cholerae (species) [taxon 666], Staphylococcus aureus (species) [taxon 1280], Staphylococcus epidermidis (species) [taxon 1282], Proteus mirabilis (species) [taxon 584], Homo sapiens (human, species) [taxon 9606], Klebsiella oxytoca (species) [taxon 571], Lodderomyces parapsilosis (species) [taxon 5480], Alternaria alternata (species) [taxon 5599], Micrococcus luteus (species) [taxon 1270]
- **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), B16F1 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0158), CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944296/full.md

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Source: https://tomesphere.com/paper/PMC12944296