# Plant-Based Nano-Delivery Systems in the Treatment of Inflammatory Disorders

**Authors:** Catarina R. Silva, Amélia C. F. Vieira, Ana Cláudia Paiva-Santos, Francisco Veiga, Gustavo Costa

PMC · DOI: 10.3390/pharmaceutics18020150 · Pharmaceutics · 2026-01-23

## TL;DR

This paper reviews how plant-based compounds, when delivered via nanotechnology, can improve treatment of inflammatory diseases by enhancing drug delivery and reducing side effects.

## Contribution

The paper compiles in vitro and in vivo evidence on plant-derived compounds in nanosystems for treating inflammation, highlighting their mechanisms and delivery systems.

## Key findings

- Plant compounds in nanosystems show improved bioavailability and reduced toxicity.
- Nanodelivery systems enhance targeting and sustained release of anti-inflammatory phytochemicals.
- Further research is needed for clinical translation of plant-based nanotherapies.

## Abstract

Inflammation is strongly related to the development of multiple chronic diseases, such as cardiovascular and autoimmune diseases, and is considered a crucial target for new therapeutic approaches, since it significantly impacts public health, contributes to high mortality rates, and decreases the quality of life. Conventional anti-inflammatory approaches are commonly used, but they present multiple limitations, such as undesirable side effects and low target-specificity. Medicinal plants and their bioactive phytochemical compounds have been studied in recent years and are considered promising alternatives to classical therapies. They are widely recognized for their capacity to modulate inflammatory pathways, regulate inflammatory responses, and consequently reduce inflammation and related symptoms. Although they are considered a good therapeutic alternative, their application in the human body is limited by certain characteristics, such as low solubility, which leads to rapid metabolism and excretion by the organism, significantly reducing bioavailability; for these reasons, the use of medicinal plants remains a biopharmaceutical challenge. Nanotechnology represents a promising tool in this context, since it can improve several characteristics of these compounds. By incorporating plant-derived compounds in nanosystems, considerable advantages, including sustained release, protection from degradation, an increase in the specificity to target tissues, and consequent reduction in toxicity, can be achieved. Thus, nanosystems promote more favorable therapeutic outcomes. This work aims to compile scientific evidence supporting the use of medicinal plants and their bioactive phytochemical compounds, incorporated in nanosystems, in inflammatory disorders. This review enlarges knowledge by integrating both in vitro and in vivo studies involving multiple medicinal plants and bioactive phytochemical compounds, describing their mechanisms of action and the nanosystems employed for drug delivery. In the future, the need for deeper mechanistic studies, the development of targeted and stimuli-responsive systems, and advancement toward clinically translatable, sustainable, and cost-effective plant-based nanotherapies is required.

## Full-text entities

- **Genes:** Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Csf3 (colony stimulating factor 3 (granulocyte)) [NCBI Gene 12985] {aka Csfg, G-CSF, MGI-IG}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Nos2 (nitric oxide synthase 2) [NCBI Gene 24599] {aka Nos2a, iNos}, Icam1 (intercellular adhesion molecule 1) [NCBI Gene 15894] {aka CD54, Icam-1, Ly-47, MALA-2}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, Nfkb1 (nuclear factor kappa B subunit 1) [NCBI Gene 81736] {aka EBP-1, NF-kB, NFKB-p50, p50}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 79240] {aka HMR, Ngfi-b, Nur77}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, Mmp2 (matrix metallopeptidase 2) [NCBI Gene 17390] {aka Clg4a, GelA, MMP-2}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, IL16 (interleukin 16) [NCBI Gene 3603] {aka LCF, NIL16, PRIL16, prIL-16}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, IL1B (interleukin 1 beta) [NCBI Gene 397122] {aka IL1B1}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, IL6 (interleukin 6) [NCBI Gene 399500] {aka IL-6}, CCL16 (C-C motif chemokine ligand 16) [NCBI Gene 6360] {aka CKb12, HCC-4, ILINCK, LCC-1, LEC, LMC}, Chil3 (chitinase-like 3) [NCBI Gene 12655] {aka Chi3l3, ECF-L, Ym1}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Slc3a2 (solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2) [NCBI Gene 17254] {aka 4F2, 4F2HC, Cd98, Ly-10, Ly-m10, Ly10}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Serpine1 (serine (or cysteine) peptidase inhibitor, clade E, member 1) [NCBI Gene 18787] {aka PAI-1, PAI1, Planh1}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 81687], IL34 (interleukin 34) [NCBI Gene 146433] {aka C16orf77, IL-34}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, CXCL5 (C-X-C motif chemokine ligand 5) [NCBI Gene 6374] {aka ENA-78, SCYB5}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Arg1 (arginase, liver) [NCBI Gene 11846] {aka AI, Arg-1, PGIF}, Ltf (lactotransferrin) [NCBI Gene 17002] {aka Csp82, Lf, MMS10R, Ms10r}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Mmp13 (matrix metallopeptidase 13) [NCBI Gene 171052], Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, TNF (tumor necrosis factor) [NCBI Gene 397086] {aka TNFSF2, TNFa}
- **Diseases:** pancreatic adenocarcinoma (MESH:D010190), fibrosis (MESH:D005355), Inflammatory Disorders (MESH:D007249), injury to (MESH:D014947), edema (MESH:D004487), ALI (MESH:D055371), pulmonary edema (MESH:D011654), Cancer (MESH:D009369), diabetes (MESH:D003920), lung damage (MESH:D008171), NAFLD (MESH:D065626), Alzheimer's Disease (MESH:D000544), AKI (MESH:D058186), obese (MESH:D009765), autoimmune diseases (MESH:D001327), hepatic steatosis (MESH:D005234), Spinal Cord Injury (MESH:D013119), Osteoarthritis (MESH:D010003), Rheumatoid Arthritis (MESH:D001172), arthritis (MESH:D001168), insulin resistance (MESH:D007333), Benign Prostatic Hyperplasia (MESH:D011470), cytotoxicity (MESH:D064420), colitis (MESH:D003092), infected (MESH:D007239), cardiovascular and autoimmune diseases (MESH:D002318), liver damage (MESH:D056486), inflammatory bowel disease (MESH:D015212), inflammatory cytokines (MESH:D000080424), chronic diseases (MESH:D002908), Ulcerative Colitis (MESH:D003093), erythema (MESH:D004890), Multiple Sclerosis (MESH:D009103), eye disorders (MESH:D005128)
- **Chemicals:** Gallic acid (MESH:D005707), auraptene (MESH:C105832), alginate (MESH:D000464), chitosan (MESH:D048271), Ibuprofen (MESH:D007052), 5-aminosalicylate (MESH:D019804), gold (MESH:D006046), NaCl (MESH:D012965), mannose (MESH:D008358), arctigenin (MESH:C071942), fat (MESH:D005223), Rutin (MESH:D012431), polymer (MESH:D011108), LPO (MESH:D008054), C (MESH:D002244), AZA (MESH:D001379), Quercetin (MESH:D011794), graphene oxide (MESH:C000628730), oridonin (MESH:C011959), PGE2 (MESH:D015232), Isoliquiritigenin (MESH:C040920), Iron (MESH:D007501), Kaempferol (MESH:C006552), CK (MESH:C112772), Diclofenac Potassium (MESH:D004008), water (MESH:D014867), lycopene (MESH:D000077276), Hyaluronic Acid (MESH:D006820), cerium (MESH:D002563), laminarin (MESH:C008247), NO (MESH:D009569), ethanol (MESH:D000431), Inulin (MESH:D007444), silver (MESH:D012834), resveratrol (MESH:D000077185), Lupeol (MESH:C010480), bruceine D (MESH:C030412), Cyclosporine A (MESH:D016572), magnesium hydroxide (MESH:D008276), silica (MESH:D012822), Bryostatin-1 (MESH:C046785), Curcumin (MESH:D003474), BD (MESH:C028491), naringin (MESH:C005274), 9AA (-), superoxide (MESH:D013481), penetratin (MESH:C414409), selenium (MESH:D012643), Celastrol (MESH:C050414), starch (MESH:D013213), nitrite (MESH:D009573), indomethacin (MESH:D007213), Cyclodextrins (MESH:D003505), polyvinyl alcohol (MESH:D011142), crocin (MESH:C029036), thiol (MESH:D013438), dexamethasone (MESH:D003907), Naringenin (MESH:C005273), Lipid (MESH:D008055), Beta-Carotene (MESH:D019207)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Thymus vulgaris (common thyme, species) [taxon 49992], Cotyledon orbiculata (species) [taxon 22999], Panax ginseng (Asiatic ginseng, species) [taxon 4054], Sus scrofa (pig, species) [taxon 9823], Danio rerio (leopard danio, species) [taxon 7955], Glycyrrhiza inflata (species) [taxon 74614], Tripterygium wilfordii (species) [taxon 458696], Homo sapiens (human, species) [taxon 9606], Syzygium aromaticum (clove, species) [taxon 219868], Gymnema sylvestre (species) [taxon 4068], Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Hypericum perforatum (species) [taxon 65561], Tinospora cordifolia (species) [taxon 285590], Anacardium occidentale (cashew, species) [taxon 171929], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Eupatorium japonicum (species) [taxon 103751]
- **Cell lines:** MiaPaCa-2 — Homo sapiens (Human), Pancreatic undifferentiated carcinoma, Cancer cell line (CVCL_0428), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), KMST-6 — Homo sapiens (Human), Transformed cell line (CVCL_2998), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), Ntra-2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038), BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12944592/full.md

## References

96 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944592/full.md

---
Source: https://tomesphere.com/paper/PMC12944592