Table 1.
Summary of descriptive characteristics of the included studies.
| Study | Intervention | Population | Outcomes | |||
|---|---|---|---|---|---|---|
| Author, Year/Country | Fruit Species/Extraction Method | Fruit Characterization Analysis | Nanoparticle Type/Production Methodology | Nanoparticle Characterization | Biological Activity Assessed/Model/Treatment Regimen | Results |
| Andréo-Filho et al., 2017/Brazil [3] |
Bixa orellana oil (commercial) |
Not evaluated | - Solid-Lipid Nanoparticles (SLN) Oil phase: octyl methoxycinnamate (OMC) or mineral oil (MO) or annatto oil (AO); - Low (heating) (P1) and high (high throughput and pressure homogenizer) energy process (P2); |
OMC (P1): −50.41 ± 4.60 mV (ZP)/1.56 μm (PS) OMC (P2): −45.26 ± 2.23 mV (ZP)/0.20 μm (PS) OMC + AO (P1): −50.29 ± 2.67 mV (ZP)/1.42 μm (PS) OMC + AO (P2): −35.74 ± 3.31 mV (ZP)/0.20 μm (PS) MO (P2): −43.20 ± 2.16 mV (ZP)/0.20 μm (PS) |
- Photoprotective efficacy (SPF) in vitro (L) with 250–450 nm wavelength range; - Skin permeation with ex vivo human abdominal skin (Franz diffusion cells); 0.01 g of OMC + AO (P1)/OMC + AO (P2)/OMC (P1)/OMC (P2); - Toxicity in 3 healthy humans (21–35 years-old); 2 mg/cm2 of OMC (P1)/OMC (P2)/MO (P2) spread in human’s forearms (MPT-FLIM skin images acquisition 0, 3 and 6 h after application); |
↓ PS in SNLs produced by high energy process; <5% of changes in PS and <10% variation of dispersion in SNLs with 5 weeks of storage; ↑ SPF value in OMC (P2) with 27.3 ± 1.2 (p < 0.05); Similar SPF values in OMC (P1), OMC + AO (P1) and OMC + AO (P2) with 22.0 ± 1.0, 19.7 ± 1.5 and 21.7 ± 1.2, respectively (p > 0.05); No significant skin permeation of SLNs with 111, 96, 93, and 82% of recoveries from OMC (P1), OMC (P2), OMC + AO (P1) and OMC + AO (P2), respectively; No changes in cellular metabolism and morphology of human skin after 6 h SLNs application; |
| Carvalho et al., 2023/Brazil [17] |
Bixa orellana oil (commercial) | 72.6 ± 0.9% of δ-tocotrienol | - Polymeric Bixa orellana Nanodispersions (PBN); - Nanoprecipitation (solvent displacement method); |
PBN: First day: 53.15 ± 0.64 nm (PS)/0.574 ± 0.032 (PdI)/18.26 ± 0.59 mV (ZP) 30th day: 59.90 ± 3.63 nm (PS)/0.574 ± 0.032 (PdI)/19.66 ± 1.45 mV (ZP) |
- Toxicity in 3-week-old Wistar rats (n = 4); Single intramuscular injection of PNB at doses of 1, 2.5, 5 and 10 mg/kg and 4% of Tween-80 as control group (clinical parameters, biochemical and hematological analysis and muscle histopathology); |
No clinical signs of PBN toxicity 4 days after injection; No muscle toxicity with 1, 2.5, and 5 mg/kg of PBN; Mild edema, hemorrhage, presence of necrotic fibers, ↑ leukocyte infiltration, and connective tissue observed in muscles with 10 mg/kg of PBN; No alterations on CPK, LDH, and myoglobin levels with 1, 2.5, and 5 mg/kg of PBN; ↑ levels of CPK, LDH, and myoglobin with 10 mg/kg of PBN (not statistically significant); No changes on erythrogram and blood lipid profile with PBN at all doses; No liver and kidney toxicity with PBN at all doses; ↑ segmented neutrophils with PBN at 2.5 and 5 mg/kg (p < 0.05); ↑ eosinophils with PBN at 1 mg/kg (p < 0.05); |
| Ferreira et al., 2021/Brazil [18] |
Bixa Orellana oil (commercial) | Not evaluated | - Nanostrutured lipid carrier (NLC) loaded with 2 and 4% (w/w) of annatto oil and 10% of CP (NLCcp2 and NLCcp4) or 10% of MM (NLCmm2 and NLCmm4) - Fusion-emulsification and ultrasonication |
NLCmm (2 and 4): ~170 to 190 nm (PS-DLS)/200 nm (PS-TEM)/~0.30 to 0.35 (PdI)/~−40 to −45 mV (ZP)/5.0 to 6.0 (pH)/Spherical morphology; NLCcp (2 and 4): ~170 to 190 nm (PS-DLS)/200 nm (PS-TEM)/~0.30 to 0.35 (PdI)/~−30 to −40 mV (ZP)/5.0 to 6.0 (pH)/Spherical morphology/78.92 ± 2.89% (EE NLCcp2)/50.54 ± 3.41% (EE NLCcp4); |
Cytotoxicity on BALB/c 3T3 (fibroblasts) and HaCaT (keratinocytes) cells (MTT 24 h); Free annatto oil and NLCcp (2 and 4) at concentrations of 25–300 µg/mL; Leishmanicidal activity in vitro with L. major internalized in RAW 264.7 macrophages (resazurin cell viability assay); Free annatto oil and NLCcp (2 and 4) at concentrations of 2 and 5 µg/mL/Amphotericin B at 0.3 and 3.125 µg/mL/Glucantime at 200 and 400 µg/mL; |
↑ PS of NLCcp2 after 90 days (p < 0.05); Phase separation of NLCmm (2 and 4) after 30 days; ↑ [ZP] on NLC with annatto oil; ↓ size variation in NLCcp4 after 90 days; NLCmm and NLCcp (2 and 4) melting points ↓ raw materials (~57 °C); Lipid crystalline nature of NLCmm and NLCcp (2 and 4) (2θ scattered angles of 7, 19, 21 and 23°); ↑ fluidity of NLCmm and NLCcp (2 and 4); No leishmanicidal activity of free annatto oil; 70–90% leishmanicidal activity of NLCcp (2 and 4); Similar leishmanicidal activity (~90%) of NLCcp 2 and 4 at 5 µg/mL (p > 0.05); ↑ leishmanicidal activity of NLCcp 2 and 4 (5 µg/mL) than glucantime (p > 0.05) No cytotoxic effect of free annatto oil on HaCaT and fibroblasts; NLCcp2 181.93 ± 8.67 µg/mL and 257.11 ± 42.11 µg/mL IC50 values on fibroblasts and keratinocytes, respectively; NLCcp4 153.64 ± 7.63 µg/mL and 123.37 ± 24.98 µg/mL IC50 values on fibroblasts and keratinocytes, respectively; |
| Gharpure et al., 2022/India [11] |
Bixa Orellana/Leaves (BL), Seeds (BS) and Seed Coats (BSc) extracts/Boiling Water extraction | - Presence of flavonoids, phenolics, and glycosides on BL, BS and BSc (UV-Vis); - Aromatics and vinyl compounds on BL/Phenolics, flavonoids, aromatics and fatty acids on BS/phenolics, steroids, flavonoids, carotenoids, fatty acid, and hydrocarbons on BSc (GC-MS); - Beta-copaene and alloaromadendrene on BL/geranylgeraniol and andrographolide on BS/octadecenal, vaccenic acid and isocarpesterol on BSc (HR-MS); - Aromatics, flavonoids, steroids, alcohols, phenolics, and alkyl groups on BL, BS and BSc (NMR); |
- Zinc Nanoparticles (ZnO) - Green synthesis with extracts of Leaves (L-ZnO), Seeds (S-ZnO) or Seed Coats (Sc-ZnO) of B. orellana follow by air-dried or calcination; |
341–353 nm (L-ZnO)/378–373 nm (S-ZnO)/327–337 nm (Sc-ZnO) before and after calcination, respectively (UV-vis absorption); 467–551 nm and 470–557 nm (L-ZnO)/468–554 nm and 469–552 nm (S-ZnO)/467–554 nm and 468–558 (Sc-ZnO) before and after calcination, respectively (PL); Spherical nanocrystallites 114–344 nm (L-ZnO)/spherical and rod-like nanocrystallites 220–440 nm and 330–660 nm, respectively (S-ZnO)/spherical and rod-like nanocrystallites 257–428 nm and 428–857 nm (Sc-ZnO) (FESEM); L-ZnO spherical (169–259 nm)/Sc_ZnO spherical (278–654 nm)/S-ZnO almond-like (220–440 nm) (TEM); 37.25 nm (L-ZnO), 37.38 nm (S-ZnO), 28.65 nm (Sc-ZnO) (XRD spectra crystallite size); 81.48% (Zn) 18.52% (O) (L-ZnO)/72.31% (Zn) 27.69% (O) (S-ZnO)/80.3% (Zn) 19.7% (O) (Sc-ZnO) (EDS); 2.301 m2/g (L-ZnO), 2.187 m2/g (S-ZnO) and 2.107 m2/g (Sc-ZnO) (BET surface area); 5 nm pores (all ZnO) (BJH); |
Anti-bacterial activity in vitro on S. aureus, B. subtilis, E. coli, and P. aeruginosa) (Well-based diffusion); L-ZnO, S-ZnO, and Sc-ZnO calcinated and uncalcinated, and free BS, BL and BSc 0.625–10 mg/mL incubated overnight; Anti-fungal activity in vitro on Penicillium sp., F. oxysporum, A. flavus, and R. solani (Well-based diffusion) L-ZnO, S-ZnO, and Sc-ZnO calcinated and uncalcinated, and free BS, BL and BSc 10 mg/mL for 4–8 days; Citotoxicity in vitro on HCT-116 cancer cell (Trypan blue staining); L-ZnO, S-ZnO, and Sc-ZnO calcinated and uncalcinated, and free BS, BL and BSc 100 µg/mL for 48 h; |
No anti-bacterial activity of free BL, BS, BSc, and calcinated ZnO nanoparticles; ↑ antibacterial potential of L-ZnO uncalcinated against S. aureus at 10, 5, and 2.5 mg/mL and B. subtilis at 10 and 5 mg/mL; ↑ antibacterial potencial of S-ZnO uncalcinated against E. coli at 10 mg/mL; ↑ antibacterial potencial of Sc-ZnO uncalcinated against S. aureus at 10 mg/mL; No anti-fungal activity and cytotoxicity of all extracts and ZnO nanoparticles; |
| Machin et al., 2019/Cuba [19] |
Bixa orellana/Seed essencial oil (AEO) Manual grinding with hydrodistillation |
Not evaluated | - Nanocochleate loaded with AEO (NCA) prepared with purified phospholipids from soy lecithin - Dehydration-hydration method; |
NCA: 52.3–96.1 nm (PS)/0.325–0.335 (PdI)/40.4 to 41.2 mV (ZP) Blank: <40 nm (PS)/0.44–0.52 (PdI)/31.1–31.3 mV (ZP) |
- Anti-amastigote activity in vitro (L. amazonensis internalized in peritoneal macrophages from BALB/c mice) (Staining with Giemsa); - Cytotoxicity in vitro on isolated peritoneal macrophages from BALB/c mice (MTT 48 h); - Anti-leishmaniasis in vivo on female healthy BALB/c mice infected with L. Amazonensis (Clinical observations of body weight and deaths and cutaneous lesions measurements); Free AEO, NCA and glucantime at 30 mg/kg by intralesional route for 4 days/4 times; |
↓ anti-amastigote activity of NCA (IC50 = 15.4 ± 1.3) compared with AEO (IC50 = 8.5 ± 0.8) (p < 0.05); ↑ cytotoxicity of free AEO (CC50 = 61.8 ± 5.9 µg/mL) compared with NCA (CC50 = 94.6 ± 2.2 µg/mL) (p < 0.05); Mortality and weight loss rates < 10% in vivo with free AEO and NCA; ↓ lesions cutaneous size in vivo with NCA compared with AEO (p < 0.05) No statistical difference on lesions cutaneous size with glucantime compare with NCA (p > 0.05) No successful leishmaniasis cure in vivo with free AEO and NCA; |
| Maitra et al., 2023/Bangladesh [10] |
Bixa orellana/Aqueous Seed extract Heating water with sodium hydroxide |
Peaks at 2930, 1615 and 1383 cm −1 (FTIR). | - Silver Nanoparticles (AgNPs) - Green synthesis with Bixa orellana seed extract |
AgNPs: 420 nm (UV-vis absorption); 2926, 1610, and 1384 cm−1 (FTIR peaks); 40–100 °C ~4% weight loss/100–380 °C ~21% weight loss/350–450 ~54% weight loss (Thermogravimetric analysis); Crystal plane/20–40 nm (PS) (TEM); 92.9 nm (PS)/0.310 (PdI) (DLS) 53% nano silver/21% oxygen/25% carbon (EDX); |
- Antioxidant activity (DPPH scavenging); AgNPs 50, 100, and 200 µg/mL for 30 min; - Antibacterial activity on S. aureus, E. coli, S. dysenteriae, and S. boydii (Disc diffusion assay); AgNPs 15, 40, and 80 µg for 24 h; - Antitumoral activity on MCF-7 (breast cancer) (MTS); AgNPs 3.90–37.25 µg/mL for 48 h; |
50.76, 62.78 and 78.86% DPPH radical scavenging of AgNPs 50, 100, and 200 µg/mL, respectively; 17 mm inhibition zone of AgNPs 80 µg dose-dependent on S. dysenteriae; 68.3% MCF-7 growth inhibition of AgNPs 31.25 µg/mL; 21.2% MCF-7 dose-dependent growth inhibition of AgNPs 3.9 µg/mL; |
| Ntohogian et al., 2018/Greece [20] |
Bixa orellana/powder and ultrafiltrated (UF) (commercial) | Presence of bixin and norbixin on annatto and UF annatto (FTIR peaks of 3400, 2920, 2855, 1690, 1603 and 1149 cm−1) ↑ crystallinity of annatto and UF annatto (XRD) No differences in FTIR spectral and XRD patterns of annatto and UF annatto; |
- Chitosan Nanoparticles (CS) loaded with 20, 40, and 60% (w/w) of annatto (CNA) and UF annatto (CNAF) - Ionotropic gelation (2:1 TPP-CS ratio) |
Blank: 250 ± 7 nm (PS)/36 ± 3 mV (ZP) CNA: 20% = 287 ± 5 nm (PS)/34 ± 3 mV (ZP)/66.40% (EE) 40% = 310 ± 8 nm (PS)/41 ± 3 mV (ZP)/68.25% (EE) 60% = 340 ± 11 nm (PS)/46 ± 3 mV (ZP)/67.25% (EE) CNAF: 20% = 263 ± 9 nm (PS)/35 ± 3 mV (ZP)/45.01% (EE) 40% = 284 ± 10 nm (PS)/40 ± 3 mV (ZP)/62.06% (EE) 60% = 303 ± 8 nm (PS)/47 ± 3 mV (ZP)/71.54% (EE) Cream-like CNA and CNAF sunscreen emulsions (CCNA and CCNAF): 5.44 to 5.88 (pH); |
Cytotoxicity on HUVE cell line (MTT 24 h); CS, Free Annatto, CNA 40% and PLA at concentrations of 100, 200, 400, 800 and 1000 mg/mL; Photoprotective efficacy (SPF) by diluted solution transmittance method; CS, CAN and CNAF 20, 40 and 60%; |
No alterations on nanoparticles morphology with different annatto %; ↑ PS from 250 to 287–340 nm with ↑ annatto %; ↑ PS from 250 to 263–303 nm with ↑ UF annatto %; CNA and CNAF were amorphous by XRD analysis; ↑ CNA yield of 70.83%; ↓ CNAF yield of 46.34%; ↑ annatto % results on ↓ CNA yield; ↑ UF annatto % results on ↑ CNAF yield; Similar low cytotoxicity of CNA and CNAF on HUVE cell line compared to PLA polyester; No signs of color alteration and phase separation of CCNA and CCNAF with 90 days of storage (−4 and 25 °C); ↑ viscosity in CCNAF 20% sunscreen emulsions with 50 to 100 rmps; ↑ SPF value of CCNA (2.63–2.24) and CCNAF (2.76–2.56) compare with blank (1.00); No ↑ on SPF of nanoparticles with ↑ on annatto and UF annatto %; |
| Santos et al., 2021/Brazil [9] |
Bixa orellana/seed extract/Solvent extraction (ethanol) | Presence of bixin and norbixin (UV-vis peaks of 353, 430, 455, and 482 nm and FTIR peaks of 1038, 989, and 845 cm−1) | - Cellulose Acetate/Annatto Nanofibers (CAAN) - Cellulose Acetate Nanofibers (CAN) - Electrospinning |
CAAN: 269 ± 101 nm (PS) 0.1% (w/w) of annatto extract CAN: 468 ± 173 nm (PS) |
Cytotoxicity by HET-CAM test (5 min) Cell proliferation in mouse (WT C57BL6) fibroblast primary culture cells (MTT 48 h) Biocompatibility and wound healing activity in Wistar rats (n = 4) 10 mm2 of CAAN subcutaneous inserted for 60 days |
2.12 ± 0.24% of annatto global extraction yield; Endothermic peak of CAAN on 100 °C; 17.2% of CAAN degree of crystallinity; 80% of CANN mass loss at 405 °C; CAAN presented smooth and flexible mats with porous interconnections; 0 irritancy index for CAAN at all time points; No cytotoxic effect of CAAN on fibroblast cells after 48 h; ↑ attachment and spread of fibroblasts on CAAN surface after 48 h; No scarring after 15 days of CAN and CAAN implantation; Presence of residual CAAN without inflammation signs 60 days post-insertion; |
| Santos et al., 2023/Brazil [21] |
Bixa orellana seed extract/Solvent extraction (ethanol) | Bixin and norbixin absorption band at 410 nm (UV-vis spectroscopy) | - Cellulose Acetate/Annatto Nanofibers (CAAN) - Cellulose Acetate Nanofibers (CAN) - Electrospinning |
CAAN: 420 ± 212 nm (PS) CAN: 284 ± 130 nm (PS) |
Cytotoxicity (MTT 2 and 7 days), cell morphology (SEM) and differentiation analysis (RT-qPCR) on myoblast cells (C2C12) 16 mm disk of CAN and CAAN |
50 ± 3° contact angle of CAAN with water = hydrophilic property; CAAN presented smooth and homogenous porous interconnections mats; ↓ nanofiber stiffnesses after adding annatto; 98% of C2C12 cell adherence on CAAN surface (no difference compared with CAN); Similar C2C12 cell viability on CAN and CAAN after 2 days; ↑ C2C12 cell viability on CAAN compared with CAN after 7 days; ↑ C2C12 cell viability on CAAN surface compared with CAN after 2 days; Aligned and elongated C2C12 cell morphology on CAN surface; Thinner and randomly distributed C2C12 cell morphology on CAAN surface; ↑ C2C12 myogenic markers (Myf5, MyoD, MyoG, and Desmin) gene expression on CAAN after 7 days compared with CAN; ↓ C2C12 myogenic markers Myf5, MyoD, Desmin, and ↑ MyoG gene expression on CAAN after 14 days compared with CAN; |
Legend: BJH = Teller, Brunauer, Emmett, Barrett, Joyner, Halenda; CC50 = 50% cytotoxic concentration; CP = cetyl palmitate; CPK = creatine kinase; DLS = Dynamic Light Scattering; DPPH = 2,2-Diphenyl-1-picrylhydrazyl; EDS = field emission scanning electron microscopy; EDX = Energy-dispersive X-ray spectroscopy; EE = Entrapment Efficiency; FESEM = Field Emission Scanning Electron Microscopy; FTIR = Fourier Transformation Infrared Spectroscopy; GC-MS = Gas Chromatography–Mass Spectrometry; HR-MS = High Resolution Mass Spectrometry; IC50 = half maximal inhibitory concentrations; LDH = Lactate dehydrogenase; MM = myristyl myristate; MPT-FLIM = Multiphoton Tomography with Fluorescence Lifetime Imaging Microscopy; MTS = 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NMR = Nuclear Magnetic Resonance spectroscopy; PdI = Polydispersivity index; PL = Photoluminescence; PLA = poly(L-lactide); PS = particle size; OMC = octyl methoxycinnamate; TEM = Transmission Electron Microscopy; TPP = Tripolyphosphate; UV-vis = Ultraviolet–visible spectroscopy; XRD = X-ray diffractometry; ZP = zeta potential; ↓ = Decrease; ↑ = Increase.