Table 1.
Various approaches to Prepare Curcumin Nanoformulations, their Composition, and Particles Evaluation
| Curcumin Nanoformulation | Method/Technique of Preparation | Composition | Particle Size (nm) and Zeta Potential (mV) | Reference |
|---|---|---|---|---|
| PLGA | Solid/oil/water (S/O/W) technique | 30 mg of PLGA polymer, 2% poly(vinyl alcohol) (PVA) and ethanol (1:1) solution, and curcumin 0.5–2 mg | 30–50 nm (TEM) ~ 100 nm (Confocal microscopy) |
[42, 43] |
| PLGA | Single emulsion–solvent evaporation | 200 mg of PLGA in 2 ml of ethyl acetate, 20 mg of curcumin, 4 ml of PVA (5%w/v), and 100 ml of PVA (0.3%w/v) | 150–200 nm (TEM and SEM) −30 to −20 mV (DLS) |
[79] |
| PLGA | Nanoprecipitation | PLGA–PEG (100 mg), drug (5 mg), and acetonitrile (10 mL) in the presence of 0.1% Pluronic F68 | 25–75 nm (SEM) 80.9 nm (DLS) −42.4 mV (DLS) |
[44] |
| PLGA | Single-emulsion/solvent-evaporation method | 20 mg of curcumin, 4 ml of 5% w/v of PVA solution, and 100 mL of 0.3% w/v PVA solution | 77±16 nm (SEM) | [80] |
| PLGA | Single emulsion (o/w)/solvent evaporation | 100 mg of PLGA and 10 mg of curcumin in dichloromethane and acetone (w/v, 10:1) in the presence of 1% (w/v) PVA aqueous solution. | 129.7±9.6nm (SEM) 0.194±0.09 (PDI) |
[81] |
| poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer |
Ring-opening polymerization | Curcumin solution in methanol was added to the solution of PLA-TPGS in dichloromethane in a polymer ratio of 1: 100 | 100 to 400 nm (SEM) The small particles are 20–40 nm in size but micrometer-sized group of several clusters |
[82] |
| Alginate nanoparticles | Alginate pre-gel nanoparticle hardening | Calcium chloride 7.5 ml of 18 mM and 0.063% of sodium alginate and chitosan 0.05% in the presence of Pluronic F127 | 100 ± 20 nm (SEM and AFM) | [83] |
| Soy protein nanoparticles | Isoelectric precipitation and diffusion | Soy protein isolate (SPI) (60 mg/ml) and curcumin (3 mg/mL) stock solution and curcumin/SPI ratio of 1:20, 1:50, or 1:100 (w/w) | 200–1000 nm (DLS) depending on the ethanol and glutaraldehyde concentrations | [84] |
| Poly(vinyl pyrrolidone) (PVP) conjugate micellae | Chemical conjugation | 1.5 g of PVP, 0.5 g of 4-dimethylaminopyridine, 1 mL of triethyl amine, and 100 mg of curcumin | 22.4 nm and 20 mV (DLS) 18.94±4.35 nm (TEM) |
[85] |
| α-cyclodextrin (α-CD) derivatives | Chemical conjugation | CD derivatives and their 2:l and 4:1-complexes with Curcumin | In between 268±16 nm and 692±53 nm depending on the ratios of conjugates and curcumin | [86] |
| β-cyclodextrin-self assembly | Inclusion complexation and self-assembly | 5, 10, 20 and 30 wt.% of curcumin in β-cyclodextrin | 50 nm small clusters to 500 nm self-assemblies (TEM) | [87] |
| Poly(β-cyclodextrin)-self assembly | Inclusion complexation and self-assembly | 5,10,20 and 30 wt.% of curcumin in poly(P-cyclodextrin) | Individual complex or assembly about 50 nm and clusters can reach up to 1 μm (TEM) | [88] |
| Casein micelle | Micelle or complexation | Casein (10 μM) in the presence of 0, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 μM curcumin | 166.3±33.1 nm (DLS) and the same was verified with SEM and AFM | [60] |
| Dextrin nanogels | Self-assembly process at 50 °C | DexC16 is composed of a hydrophilic dextrin backbone with grafted acrylate groups, which are partially substituted with long alkyl chains (SC16). DexC16 (0.008 mg/ml) and the curcumin (10, 30, 50 μM) | 61.1 nm in water and 59.2 in PBS solution (DLS) (freshly prepared samples) Size does not change much in 12 days in water (58.7 nm) but in PBS it increases to 100 nm |
[89] |
| Thermosensitive polymer nanoparticles | Redox-free radical polymerization | 1.8 g monomer, cross-linker (N′, N′-methylene bisacrylamide), 100 mg PEG-ester, initiator/activator and curcumin 20 wt.% loading | ~ 132 nm and −1.46 mV (DLS) | [50, 90] |
| Thermosensitive polymer nanoparticles | Free-radical polymerization | Curcumin (5 mg in 0.1 ml ethanol) and polymer (chitosan-PNIPAM, 50 mg in 5 ml 1% acetic acid) with 100 μl 0.05% TPP solution | 100–300 nm (DLS) SEM analysis of curcumin loaded TRC-NPs revealed a size range of 180–220 nm |
[51] |
| O/W nanoemulsions | High-pressure homogenization | Medium chain triacylglycerols (oil), tween 20, and curcumin | 79.5–174.3 nm(DLS) | [57] |
| Sub-micrometer dispersions | Moschwitzer’s method by high-speed homogenization | Curcumin suspensions in water (1%) were subjected to premilling treatments to reduce curcumin particle sizes to the micrometer range according to Moschwitzer’s method by high-speed homogenization at pressure levels ranging from 50 to 200 MPa and for up to 40 HPH cycles | 2000, 1000–600 nm (SEM) | [91] |
| Self-emulsifying drug delivery system | Self-emulsification | 57.5% surfactant (emulsifier OP: Cremorphor EL, 1:1), 30% co-surfactant (PEG 400) and 12.5% oil (ethyl oleate). It improves curcumin solubility to 21 mg/g | ~ 3.3 nm (DLS) | [56] |
| Nanoprecipitation | Syringe driven filter nanoprecipitation | Curcumin/ethanol solution with antisolvent water was done in a micromixer [poly(methyl methacrylate)] | The nanoprecipitate first formed as amorphous 30–40 nm nanoparticles, then their amorphous aggregates (~140 nm after 10 min and ~ 200 nm after 90 min), and finally became dendritic aggregates of needle-shaped curcumin crystals (SEM) | [71] |
| Nanoprecipitation | Droplet controlled nanoprecipitation | Curcumin/ethanol solution (0.2, 0.4, 0.8, 1.6, and 2.0 gl−1) | 450–210 nm (SEM) | [70] |
| Lipid nanospheres | Vesicle formation | Soybean oil (10 mg/ml) and DMPC:PEG-DSPE (10/1/0.06 molar ratio) | 187±53 to 217±93 nm (DLS) | [58] |
| Liposomal formulation | Curcumin decoration on liposomes using click chemistry | Dipalmitoylphosphatidylcholine/Chol(2:l) liposomes incorporating 10–20% curcumin conjugate | 52.8±5.5 to 207.2 ± 8.0 with zetapotential between −7.6±1.7 and −24.3±1.7mV depending on the liposome modifications (DLS) | [59] |
| Superparamagnetic silica reservoirs | Composite | Fe3O4, nanoparticles (37% wt) and curcumin (30% wt) into the porous silica matrix | Fe3O4 core diameter 7.13 nm (variance = l.89 nm) curcumin shell 2.59±0.07 nm (SAXS) Curcumin and Fe3O4, nanoparticle containing silica particles were ellipsoidal in shape and the size of the particles ranged from 200 nm to 1 μm. |
[92] |
| Magnetic nanoparticles | Nanoparticle coating with stabilizer or polymers | Fe3+/Fe2+ ratio of 2:1, chitosan or oleic acid | 300 nm and 500 nm (DLS and TEM/SEM). | [93] |
| Magnetic poly(lactic acid) microspheres | Oil-in-water emulsion | 1% (w/v, 50 ml) of PVA, Fe3O4 nanoparticles (5 mg), PLA (50 mg), PEG (20 mg), and curcumin (5 mg) | 0.55 to 0.75 (μm (DLS and SEM) | [94] |
| Hollow capsules | Layer by layer assembly | Melamine formaldehyde templates coated with six double layers of poly(sodium 4-styrene sulfonic acid) and poly(ethylene imine) and 4.5 mg/mg of microcapsules | 2.2 to 2.8 μm (DLS) | [95] |
| Silk fibroin and chitosan blend | Capillary microdot technique | Silk fibroin: chitosan with compositions of 100:0; 25:75; 50:50; 75:25) | <100 nm(TEM) 50:50 SFCS (130 ± 4.2 nm) (TEM) |
[96] |
| Dendrasome | Diffusion | Dendrosome and curcumin ratio 25:1 | 200–500 nm (UV-microscope) | [47] |
| Albumin nanosuspension | Solvent evaporation | Not available | 245.2 nm (DLS) | [97] |
AFM – Atomic force microscopy; DLS - Dynamic light scattering method; DMPC - l,2-Dimyristoyl-sn-glycero-3-phosphochlorine; PEG-DSPE - l,2-distearoyl-sn-glycero-3-phosphoehanolamine-N-[monomethoxy poly(ethylene glycol); PLA - Poly(lactic acid); PVA - Poly(vinyl alcohol); SA - L-glutamic acid, N-(3-carboxyl-l-oxopropyl)-, 1,5-dihexadecyl ester; SAXS – Side angle X-ray spectroscopy; SEM – Scanning electron microscopy; TEM - Transmission electron microscopy.