A Critical Review of the Use of Surfactant-Coated Nanoparticles in Nanomedicine and Food Nanotechnology

Figures & data

Figure 1 Classification of surfactants and structures of the ionic and nonionic surfactants mentioned in this review.

Figure 2 (A) Typical Illustration of surfactant-coated nanoparticles. (B) Various organic and inorganic materials used in the core of surfactant-coated nanoparticles.

Figure 3 (A) Equations of the DLVO theory. (B) Relationship between two particles assuming the DLVO theory. (C) A typical example of potential energy presented in the DLVO theory.

Notes: (A) Data from Hamley⁶³ and Ohshima.⁶⁵

Table 1 Summary of Surfactant-Coated Nanoparticles Used in the Field of Nanomedicine

Target	Type of Surfactant	Core Material	Size	Encapsulated Compound	In vitro	In vivo	Main Conclusions	References
Selective adsorption of plasma protein on the surface	Polysorbates (20, 40, 60 and 80)	Lipid	Around 600 nm		In vitro protein absorption model		Lipid nanoparticles coated with polysorbate 80 had increased adsorption of apolipoprotein E (ApoE) on their surface.	[^Citation382]
Suppression of plasma protein adsorption on the surface	Poloxamer 188	PLGA	Below 200 nm		In vitro protein absorption model		Various surfactant concentrations were studied and the inhibition of protein adsorption on the nanoparticles was most effective when incubated with PLGA at a concentration of 0.5% poloxamer 188. PLGA nanoparticles coated with poloxamer 188 inhibited albumin adsorption on the surface by 50% compared to bare nanoparticles.	[^Citation383]
	Poloxamer 407	PLA, PCL, PMMA, 50: 50 blend of PLA: EVA	35–45 μm		Neutrophils collected from human blood		Various poloxamer188 coated nanoparticles consisting of four different cores (PLA, PCL, PMMA, and PLA:EVA=50:50) were prepared. In any group of nanoparticles with any core, the adsorption of opsonin was inhibited by covering the surface with poloxamer 407.	[^Citation384]
Investigation of the mechanism of tissue distribution	Polysorbate 80	PLGA	259 ± 62 nm	β-carotene		Male Sprague Dawley rats (12 weeks of age, 410–580 g body weight, intravenous administration)	Polysorbate 80 coated PLGA nanoparticles containing β-carotene accumulated in lung, rather than brain.	[^Citation176]
	Poloxamers (184, 188, 407,338), poloxamine 908, polysorbates (20, 60, 80), brij 35	Poly (methyl methacrylate)^14C labeled	131 ± 30 nm			Male and female Wistar rats (180–200 g body weight, intravenous administration)	In all the groups of surfactants used in the study, the coating of surfactants on the nanoparticles reduced their accumulation in the liver. And they were found to increase uptake into other organs in the body, including the heart, gastrointestinal tract, ovaries, kidneys, muscles and brain.	[^Citation385]
Wound healing	Poloxamer 407	Gold	29.2 ± 2.1 nm			Female Wister rats (180–230 g body weight, topical application)	PEG-AuNPs loaded into poloxamer 407 hydrogel was affected gene expression of several inflammatory and anti-inflammatory mediators.	[^Citation386]
Anti-Influenza activity	Dodecyltrimethylammonium bromide (DDAB)	Silica	80 nm		Influenza A (H1N1), MDCK cells, Candida albicans, Staphylococcus aureus, Escherichia coli		The DDAB coated silica nanoparticles showed high anti-Influenza and antibacterial activity. The interaction between DDAB and silica was maintained in water for 60 days. No antibacterial activity was observed in “medium only” after incubated with DDAB coated silica nanoparticles. This result suggests that this antibacterial activity is not the surfactant itself released from the nanoparticles.	[^Citation387]
Safety assessment	Polysorbate 80	Chitosan	251 ± 15 nm	Rhodamine B isothiocyante		Sprague-Dawley male rats (180–220 g body weight, 7 weeks old, intravenous administration)	Toxicity assessments were performed in rat brain 7 days after treatment with poloxamer 80 coated nanoparticles. The results showed that a dose of nanoparticles showed body weight loss and dose-dependent neuronal apoptosis, a slight inflammatory response in the frontal lobe, and down-regulation of GFAP expression in the cerebellum.	[^Citation388]
Enhancement of the intracellular imaging function of fluorophores	Poloxamer 188		Below 100 nm	BF2-chelated azadipyrromethene (NIR-AZA) fluorophores	Fixed HeLa-Kyoto cells		Poloxamer 188 worked as useful tool for intracellular imaging vehicle of BF2 chelated azadipyrromethene (NIR-AZA) fluorophores.	[^Citation389]
Enhancement of near‐infrared fluorescence (NIRF) and positron emission tomography (PET) imaging	Poloxamer 407	Tannic acid	140 nm	IR-780 iodide dye	L929 cells, SKBR3 cells	SKBR3 tumor bearing mice (intravenous administration)	The nanoparticles formed by the self-assembly of poloxamer 407 and tannic acid accumulated in the tumor in vivo and were biocompatible. These nanoparticles containing the IR-780 iodide dye found to be useful for NIRF and PET imaging.	[^Citation390]
Cancer diagnosis in magnetic resonance imaging	Folic acid-poloxamer 407 conjugate	SPION	180–190 nm		KB cells		SPION nanoparticles coated with Folic acid-poloxamer 407 conjugate were prepared. It was confirmed that these nanoparticles have an active targeting ability to folic acid receptors in vivo and are useful for imaging cancer tissues.	[^Citation391]
Enhancement of anti-cancer activity	Polysorbate 20	Silver	Around 5 nm		HEK293T cells, MDA-MB-231 cells		Silver nanoparticles coated with polysorbate 80 and albumin or hemoglobin were prepared. Prepared nanoparticles exhibited increased biocompatibility and selective toxicity to cancer cells. Furthermore, they enhanced the photosensitizing effect of the fluorescent material bound to the nanoparticles, which could be applied to photochemotherapy.	[^Citation392]
Enhancement of anti-cancer activity	Polysorbate 80	Lipid	652.5 ± 3.52 nm	Vitamin C (Ascorbic acid)	H-Ras 5RP7 cells, NIH/3T3 cells		Compared to bare vitamin C, vitamin C encapsulated in solid lipid nanoparticles coated with polysorbate 80 was taken up more by cancer cells. In addition, nanoparticles enhanced the anti-cancer activity of encapsulated vitamin C.	[^Citation393]
Enhancement of anti-cancer activity	Polysorbate 80	PLGA	247 ± 1 nm	Rapamycin	C6 cells		Rapamycin-encapsulated PLGA nanoparticles coated with polysorbate 80 were prepared. Coating nanoparticles with polysorbate 80 increased their uptake into glioblastoma cells. Polysorbate 80 blocked or inhibited the P-glycoprotein, thus preventing rapamycin efflux and providing enhanced cellular uptake.	[^Citation394]
Enhancement of anti-cancer activity	Poloxamer 188	Sericin	200–400 nm	Resveratrol	CRL-2522 cells, Caco-2 cells		Resveratrol-containing sericin nanoparticles coated with poloxamer 188 were prepared. Nanoparticles were non-toxic to normal cells, but toxic to cancer cells.	[^Citation395]
Enhancement of anti-cancer activity	Poloxamer 188	PLGA	217.6 ± 8.6 nm	Docetaxel	MCF-7 TAX30 cells		PLGA nanoparticles coated with poloxamer 188 showed higher concentrations of cell uptake and faster release of encapsulated drug compared to bare nanoparticles.	[^Citation396]
Enhancement of anti-cancer activity	Poloxamer 188	PLGA	179.4 ± 11.2 nm	Paclitaxel	MCF-7 cells, Colo-205 cells		PLGA nanoparticles coated with poloxamer 188 showed strong anti-cancer activity compared to bare paclitaxel.	[^Citation397]
Enhancement of anti-cancer activity	Polxamer 188, D-α-tocopheryl polyethylene glycol 1000 succinate, sodium cholate	PLGA	Various particle sizes from 100–500 nm	Epirubicin	SK-MES-1 cells		Various nanoparticles of 100–500 nm covered with Polxamer 188, D-α-tocopheryl polyethylene glycol 1000 succinate, sodium cholate and poly vinyl alcohol, respectively, were prepared. The cholic acid-coated nanoparticles had the smallest particle size and thus exhibited the strongest anticancer effect of the encapsulated epirubicin.	[^Citation398]
Enhancement of anti-cancer activity	Folic acid-poloxamer 407 conjugate	Vegetable oil	77.18 ± 1.27 nm	Hoechst, Dil	BJ5ta cells, Hela cells		Vegetable oil nanoparticles modified with Folic acid-poloxamer 407 conjugate showed higher uptake into cancer cells and drug release at lysosomes compared to PEGylated albumin-based nanoparticles.	[^Citation399]
Enhancement of anti-cancer activity	Methotrexate-poloxamer 407 conjugate, folic acid-poloxamer 407 conjugate	Vegetable oil	91.3 ± 24.4	Methotrexate	Caco-2 cells		Vegetable oil nanoparticles coated with methotrexate-poloxamer 407 conjugate showed a stronger anticancer effect compared to the group coated with Folic acid-poloxamer 407 conjugate.	[^Citation400]
Enhancement of anti-cancer activity	Polysorbate 80	Poly (butyl cyanoacrylate)	210 ± 10.01 nm	Doxorubicin		Male Wistar rats imigrated glioblastoma tissue (intraperitoneal administration)	Rats administered with polysorbate 80 coated poly (butyl cyanoacrylate) nanoparticles containing doxorubicin survived for more than 180 days (post tumor implantation).	[^Citation401]
Enhancement of anti-cancer activity	Poloxamer 188	Human IgG	140.2 ± 2.4 nm			Albino male Wistar rats (160–180 g), metastatic models of chemically induced non-small cell lung cancer (intravenous administration of A549 cells)	Nanoparticles consisting of human IgG and poloxamer 188 were prepared by encapsulating siRNA. In addition, anti-NTSR1-mAb was used to induce them into cancer cells. It was confirmed that nanoparticles were accumulated in the cancerous tissue of the mouse body. On the other hand, naked siRNA disappeared from the bloodstream in a short time after administration.	[^Citation402]
Enhancement of anti-cancer activity	Polysorbate 80	Poly (butyl cyanoacrylate)	246 ± 11 nm	Doxorubicin		Male Wistar rats immigrated glioblastoma tissue (200–240 g body weight, intraperitoneal administration)	Rats administered with polysorbate 80 and poloxamer 188 coated poly (butyl cyanoacrylate) nanoparticles containing doxorubicin survived for more than 181 days (post tumor implantation).	[^Citation403]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	300 nm	Rhodamine 6G	Primary endothelial cells isolated from human brain tissue		Compared to bare nanoparticles, coating nanoparticles with polysorbate 80 increases their uptake into cells by 20 times.	[^Citation404]
Brain delivery	Poloxamers (184, 188, 338, 407), poloxamine 908, polysorbates (20, 80), polyoxyethelene	Poly (methyl methacrylate)	215 ± 44 nm		Bovine microvessel endothelial cells		Nanoparticles coated with Polysorbate 80 resulted in increased accumulation or uptake in bovine microvessel endothelial cell compared to other surfactant coated nanoparticles.	[^Citation405]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	270 nm	Doxorubicin		Wistar rats (180–200 g body weight, intravenous administration)	Compared to bare doxorubicin, polysorbate 80-coated poly (butyl cyanoacrylate) nanoparticles increased the brain concentration of doxorubicin by more than 60 times.	[^Citation406]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	189.7 ± 7.6 nm	Doxorubicin		Male Wistar rats (200–220 g body weight, intravenous administration)	Poly (butyl cyanoacrylate) nanoparticles coated with polysorbate 80 and encapsulated with doxorubicin significantly increased the transcytosis of doxorubicin into the postcapillary parenchymal compartment compared to bare particles or surfactants alone.	[^Citation407]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	70, 170, 220 and 345 nm	Methotrexate		Male Sprague-Dawley rats (200–230 g body weight, intravenous administration)	Among the poly (butyl cyanoacrylate) nanoparticles coated with polysorbate 80 had a particle size of 70, 170, 220, and 345 nm. Nanoparticles whose diameter is 70 nm was the most effectively to transport into brain.	[^Citation408]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	35.58 ± 4.64 nm	Tacrine		Wistar rats (180–220 g body weight, intravenous administration)	Coating poly (butyl cyanoacrylate) nanoparticles containing tacrine with polysorbate 80 increased the accumulation of tacrine in the brain compared to bare nanoparticles.	[^Citation409]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	230 nm	Hexapeptide dalargin		Male ICR mice (20–22 g body weight, intravenous administration)	Polysorbate 80 coated nanoparticles strongly interacted with the brain blood vessel endothelial cells of mice. In addition, intravenous injection of nanoparticles encapsulating hexapeptide daralgin and coated with polysorbate 80 into mice was found to have an analgesic effect. In contrast, no analgesic effect was observed in the control group (mixture of drug, nanoparticles, surfactant).	[^Citation410]
Brain delivery	Polysorbate 80	Poly (butyl cyanoacrylate)	N/A	Nerve growth factor (NGF)		Male C57B1/6 mice (22–24 g body weight, 3 months old, intraperitoneal administration), Parkinson’s disease symptoms were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse.	Polysorbate 80-coated poly (butyl cyanoacrylate) nanoparticles with nerve growth factor adsorbed on the surface were prepared. Symptoms of the Parkinson’s disease were reduced in the nanoparticles dose group. This effect persisted after 7 and 21 days after of dosing.	[^Citation411]
Brain delivery	Polysorbate 80	PLGA	N/A	Brain derived neurotrophic factor (BDNF)		Male C57BL/6N mice (25–28 g body weight, 11–13 weeks old, intravenous administration), weight-drop traumatic brain injury models	Polysorbate 80-coated PLGA nanoparticles with brain-derived neurotrophic factors adsorbed on the surface were prepared. In the nanoparticle-administered group, the concentration of neurotrophic factors in the brain increased, and the decline in cognitive function caused by traumatic brain injury was suppressed.	[^Citation412]
Brain delivery	Polysorbate 80	SPION	11.5 ± 2.2 nm			Adult female Sprague–Dawley rats (250–300 g body weight, intravenous administration)	Polysorbate 80, polyethylene glycol (PEG), polyethylene imine (PEI), coated SPION nanoparticles were prepared. PEG and PEI allowed further absorption of Tween 80 on the surface of the nanoparticles. Rats were injected nanoparticles by tail vein injection, and when magnetized, they crossed the blood-brain barrier and localized to the brain.	[^Citation413]
Brain delivery	Polysorbate 80	Lipid	219.9 ± 15.6 nm	Erythropoietin		Albino male Wistar rats (160–180 g body weight, intraperitoneal administration), Amyloid β-protein injected cognitive deficit model	Lipid nanoparticles coated with polysorbate 80 and further encapsulated with erythropoietin were prepared. Experimental results from the Morris water maze test showed that the cognitive deficits were predominantly recovered in the nanoparticle administrated group compared to the free drug group.	[^Citation414]
Brain delivery	Polysorbate 80	Gold	50–90 nm	Donepezil		Adult wild AB type zebrafish (about 1.5 years old, oral dose)	Gold nanoparticles coated with polysorbate 80, PEG and further conjugated with donepezil were prepared. After 15 days of oral administration, acetylcholinesterase inhibitory activity was observed in the treated group of the prepared nanoparticles. Localization of the nanoparticles to the brain was also observed as the number of days of administration increased.	[^Citation415]
Brain delivery	Polysorbate 80, poloxamer 188	PLGA	Various particle sizes below 250 nm	Doxorubicin, loperamide		Male Wistar rats (180–220 g body weight), female ICR (CD1) mice (23–28 g body weight), female Balb/c mice (20–25 g body weight), intraperitoneal administration	Doxorubicin or loperamide-loaded PLGA nanoparticles coated with poloxamer 188 and polysorbate 80 entered to the brain.	[^Citation416]
Brain delivery	Polysorbate 80 and other 11 different surfactants	Poly (butyl cyanoacrylate)	230 nm	Dalargin		Male ICR mice (20–22 g body weight, intravenous administration)	Polysorbate 80 coated nanoparticles enabled the highest induction of analgesia compared to other surfactant coated nanoparticles.	[^Citation417]

Abbreviations: BJ5ta cells, hTERT-immortalized foreskin fibroblast cells; C6 cells, rat glioma cells; CRL-2522 cells, human fibroblast cell lines; Caco-2 cells, human colorectal adenocarcinoma cells; Colo-205 cells, human colon adenocarcinoma cells; DDAB, dodecyltrimethylammonium bromide; EVA, poly(ethylene-co-vinyl acetate); H-Ras 5RP7 cells, H-ras transformed carcinogenic rat embryo fibroblast cell lines; HEK293 cells, human embryonic kidney cells 293; Hela cells, human cervical carcinoma cells; KB cells, human epidermoid carcinoma cells; L929 cells, mouse fibroblast-like cells; MCF-7 TAX30 cells, MCF-7 docetaxel-resistant sublines; MCF-7 cells, human breast cancer cells; MDA-MB-231 cells, human breast cancer cells; MDCK cells, Madin-Darby canine kidney cells; NIH/3T3 cells, mouse fibroblast-like cells; NPs, nanoparticles; PCL, poly(ε-caprolactone); PEG, polyethylene glycol; PLA, poly lactic acid; PLGA, poly(lactic-co-glycolic acid); PMMA, Poly(methyl Methacrylate); SK-MES-1 cells, human Lung squamous cell carcinoma cells; SKBR3, human breast adenocarcinoma cells; poloxamer, copolymer of polyoxyethylene and polyoxypropylene; poloxamine, polyalkoxylated symmetrical block polymers of ethylene diamine; polysorbate, polyoxyethylene sorbitan monooleate.

Figure 4 Behavior and fate of surfactant-coated nanoparticles in the blood stream.

Notes: (A) Bare nanoparticles. (B) Poloxamer 188 coated nanoparticles. (C) Polysorbate 80 coated nanoparticles.

Figure 5 Active and passive targeting of nanoparticles to the cancer cells.

Notes: (A) Normal vasculature. (B) Passive targeting in tumor vasculature. (C) Active targeting in tumor vasculature. (D) Types of active targeting ligands for nanoparticles and its considerations for optimization of their efficacy. Notes: (B, C) Adapted from Tran S, DeGiovanni P, Piel B, et al. Cancer nanomedicine: a review of recent success in drug delivery. Clin Transl Med. 2017;6(1):44. doi:10.1186/s40169-017-0175-0.¹⁵³ (D) Adapted from Advanced Drug Delivery Reviews, 143, Alkilany AM, Zhu L, Weller H, et al, Ligand density on nanoparticles: a parameter with critical impact on nanomedicine, 22–36, Copyright 2019, with permission from Elsevier.¹⁵⁸

Table 2 Summary of Surfactant-Coated Nanoparticles Used in the Field of Food Nanotechnology

Target	Type of Surfactant	Core Material	Size	Encapsulated Compound	In vitro	In vivo	Main Conclusions	References
Enhancement of stability of encapsulated food components	Polysorbate 20	Lipid	10–20 nm	β-carotene	Water		The preparation of lipid nanoparticles coated with polysorbate 20 was optimized by combining the response surface method (RSM) and central composite design (CCD). Furthermore, the β-carotene encapsulated within the nanoparticles was protected from degradation in water.	[^Citation418]
Enhancement of stability of encapsulated food components	Polysorbate 80, sorbian monolaurate	Lipid	235 ± 16 nm	Quercetin	In vitro gastrointestinal tract model		Solid lipid nanoparticles coated with Polysorbate 80 and Span 20 were prepared. Furthermore, quercetin encapsulated in the nanoparticles showed improved release profiles and bioaccessibility under the conditions of the gastrointestinal fluid model and intestine model.	[^Citation419]
Enhancement of stability of encapsulated food components	Poloxamer 188	PLGA	154 ± 12 nm	Picrorhiza kurroa extract	PBS Buffer		PLA nanoparticles coated with poloxamer 188 were prepared. It showed a sustained release of encapsulated picrorhiza kurroa extracts.	[^Citation420]
Enhancement of stability of encapsulated food components	Poloxamer 188	Chitosan	414.8 ± 333.8 nm	Epigallocatechin-3-gallate	Water		Succeeded in encapsulating catechin in the chitosan nanoparticles by using poloxamer 188 in the preparation.	[^Citation421]
Enhancement of stability of encapsulated food components	Poloxamer 407	Cocoa butter	77 nm	Conjugated linoleic acid	Water		Poloxamer 407 coated solid lipid nanoparticles enhanced the oxidative stability of the encapsulated conjugated linoleic acid in water. Conjugated linoleic acid in solid lipid nanoparticles was also found to be more stable for thermal processes such as pasteurization.	[^Citation422]
Enhancement of stability of encapsulated food components	Poloxamer 407	Lipid	Below 200 nm	Lutein	Water		Lipid nanoparticles coated with poloxamer 407 were prepared. The lutein encapsulated within the nanoparticles was protected from degradation in water. The water dispersibility and antioxidant activity of the encapsulated lutein were also increased.	[^Citation423]
Enhancement of stability of encapsulated food components	Poloxamer 407	Lipid	100–110 nm	Omega-3 fish oil, α-tocopherol	Water		Poloxamer 407 coated solid lipid nanoparticles enhanced the oxidative stability of the encapsulated ω3 fatty acids in water. This effect was further enhanced when α-tocopherol was co-encapsulated.	[^Citation424]
Enhancement of stability of encapsulated food components	Sophorolipid	Zein	Around 200 nm	Lutein	Water		Zain nanoparticles coated with sophorolipid were prepared. The lutein encapsulated in the nanoparticles was protected from degradation in water. The water dispersibility of the encapsulated lutein was improved 80-fold compared to the bare lutein group.	[^Citation425]
Enhancement of stability of encapsulated food components	Rhamnolipid	Propylene glycol alginate	228 nm	Curcumin	In vitro gastrointestinal tract model		Curcumin nanoparticles coated with rhamnolipid formed a complex with propylene glycol alginate, which increased the photostability and bioaccessibility of curcumin in an in vitro small intestine model.	[^Citation426]
Enhancement of stability of encapsulated food components	Rhamnolipid	Propylene glycol alginate	135.10 ± 2.87 nm	Coenzyme Q10, Resveratrol	In vitro gastrointestinal tract model		Zein nanoparticles coated with rhamnolipid formed nanoparticle complexes with propylene glycol alginate. Furthermore, coenzyme Q10 and resveratrol encapsulated in the nanoparticles enhanced its stability under the conditions of the in gastrointestinal fluid.	[^Citation427]
Elucidation of the intestinal transport mechanism of nanoparticles	Polysorbate 80, poloxamer 188	Lipid	247 ± 4 nm		Caco-2 cells		Solid lipid nanoparticles coated with polysorbate 80 and poloxamer 188 were taken up by Caco-2 small intestinal epithelial cells via both the clathrin and cabelaic pathways. Furthermore, the efflux activity of P-gp was inhibited.	[^Citation428]
Increase of the penetration in mucus	Pluronics (P65, F38, P103, P105, F68), poloxamer 407	PLGA, poly (ε-caprolactone)	Approximately 100 nm		Human mucus model using human cervicovaginal mucus		Surfactant-coated nanoparticles showed a significant increase in dispersion in mucus. Among them, poloxamer 407 was most effective.	[^Citation310]
Increase of bioavailability of food components	Polysorbate 80	Lipid	132.9 nm	Vitamin D3 (Cholecalciferol)	In vitro gastrointestinal tract model		Nanostructured lipid carriers coated with polysorbate 80 improved the stability of encapsulated vitamin D3 in the gastric juice. On the other hand, the release of vitamin D3 was observed in the intestinal fluid environment in vitro.	[^Citation429]
Increase of bioavailability of food components	Polysorbate 80	Poly-γ-glutamic acid	Around 50 μm	Indomethacin		Male Jcl:ICR mice (5 weeks of age, oral dose)	Poly-γ-glutamic acid nanoparticles coated with polysorbate 80 increased the AUC by oral administration of encapsulated indomethacin.	[^Citation430]
Increase of bioavailability of food components	Polysorbate 80	Galactosylated PLGA	150 nm	Resveratrol	Caco-2 cells	Sprague-Dawley rats (220 ± 20 g, oral dose)	Polysorbate 80 coated PLGA nanoparticles enhanced the bioavailability of encapsulated resveratrol. Galactosylation of PLGA further increased its uptake via sodium glucose-binding transporter 1 (SGLT1).	[^Citation431]
Increase of bioavailability of food components	Poloxamer 407	Lipid	Below 100 nm	Vitamin D3 (Cholecalciferol)		Male Wistar rats (oral dose)	Poloxamer 407 coated solid lipid nanoparticles showed a stable size distribution of the particles. The bioavailability of vitamin D3 encapsulated in the solid lipid nanoparticles was improved.	[^Citation432]
Increase of bioavailability of food components	Poloxamer 407	Hydroxypropyl methylcellulose	Below 300 nm	Trans-resveratrol		Male Sprague-Dawley rats (oral dose)	Poloxamer 407 coated hydroxypropyl methylcellulose nanoparticles enhanced the oral and transdermal absorption of encapsulated trans-resveratrol.	[^Citation433]
Increase of bioavailability of food components	D-α-tocopheryl polyethylene glycol 1000 succinate	Curcumin	12.3 ± 0.1 nm		HT-29 cells, in vitro gastrointestinal tract model	Male Wistar rats (200 ± 20 g, oral dose)	Curcumin nanoparticles coated with D-alpha-tocopheryl polyethylene glycol 1000 succinate released curcumin in the in vitro colon environment and showed toxicity to colon cancer cells. Compared to bare curcumin, localization of curcumin in the colon environment for a longer period of time was confirmed in vivo.	[^Citation434]
Increase of bioavailability of food components	Propylene glycol monolaurate (Lauroglycol fcc), caprylocaproyl polyoxyl glycéride (Labrasol)	Curcumin	Below 200 nm			Sprague-Dawley rats (250 ± 20 g, oral dose)	Curcumin nanoparticles covered with lauroglycol fcc (oil) and labrasol (surfactant) were prepared. Compared to the bare curcumin, AUC of curcumin was increased by 7.6 times in nanoparticle-encapsulated curcumin in vivo.	[^Citation435]
Increase of bioavailability of food components	Kolliphor HS 15	Lipid	N/A	Curcumin		Male Sprague-Dawley rats (240–280 g, oral dose)	Kolliphor increased the dispersion of curcumin encapsulated solid lipids in water. Furthermore, it increased the amount of curcumin transferred into the bloodstream via oral administration.	[^Citation436]
Increase of bioavailability of food components	Saponin	Curcumin	52–109 nm		In vitro gastrointestinal tract model	Male Sprague-Dawley rats (260–300 g, oral dose)	Curcumin nanoparticles coated with saponin were prepared. saponin-coated nanoparticles have improved physicochemical stability and storage time. Compared to the bare curcumin, AUC of curcumin was increased by 8.9 times in nanoparticle-encapsulated curcumin in vivo.	[^Citation437]
Supplements for alleviate Zn deficiency	Poloxamer 188	Poly (butyl cyanoacrylate)	Approximately 100 nm	Green tea extract, zinc	EBM2 cells		Green tea extract and Zn encapsulated with Poly (butyl cyanoacrylate) nanoparticles and coated with poloxamer 188 were found to have a controlled release of encapsulated Zn ions, antioxidant activity and biocompatibility.	[^Citation438]
Enhancement of the nutritional value of dairy products	Poloxamer 188	Lipid	243.7 ± 9.46–394.6 ± 4.05 nm	Lipoic acid		Anemia induced rats (oral dose)	Encapsulation of lipoic acid into solid lipid nanoparticles coated with poloxamer 188 enhanced the sustained release of lipoic acid in vitro. Furthermore, it inhibited the decrease in erythrocyte and hemoglobin concentrations in anemia-induced rats.	[^Citation439]
Enhancement of antibacterial activity	Polysorbate 80, sodium dodecyl sulfate	Silver	Approximately 26 nm		10 bacterial strains		Polysorbate 80 and SDS modified silver nanoparticles show a significant increase in antibacterial activity	[^Citation348]
Enhancement of antibacterial activity	Polysorbate 80	Lipid	115.6–115.8 nm	Menthol	Escherichia coli, Staphylococcus aureus, Bacillus cereus, Fungi (Candida albicans)		Menthol-loaded solid lipid nanoparticles exerted stronger antimicrobial activity against fungi than bacteria. Menthol-loaded solid lipid nanoparticles exerted more efficient against Gram-positive bacteria than Gram-negative bacteria.	[^Citation440]
Enhancement of antibacterial activity	Poloxamer 188	Lipid	177.2 ± 3.99 nm	Furosemide silver complex	Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa		Encapsulation of Furosemide silver complex into poloxamer 188 coated nanoparticles enhanced the sustained release of Furosemide silver complex (sustained release of Ag-FSE for more than 96 h) and significantly improved its antimicrobial effect.	[^Citation441]
Enhancement of antibacterial activity	Poloxamer 188	PLGA	158 nm	Curcumin	Escherichia coli, Staphylococcus aureus, Salmonella, Pseudomonas aeruginosa, Bacillus sonorensis, Bacillus licheniformis		The encapsulation of curcumin into the nanoparticles increased the dispersion of curcumin in water. Curcumin-loaded solid lipid nanoparticles coated with poloxamer 188 found to have higher in in vitro antimicrobial properties.	[^Citation442]
Enhancement of antibacterial activity	Poloxamer 407	PLGA	Approximately 290 nm	Antimicrobial peptides	Escherichia coli O157:H7 and Methicillin resistant Staphylococcus aureus		PLGA nanoparticles coated with poloxamer 407 enhanced the antimicrobial activity of the encapsulated peptides by several times.	[^Citation443]
Enhancement of antibacterial activity	Poloxamer 407, poloxamer 188	Silver sulfadiazine	369 nm		L929 cells, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa		The hydrogel (containing poloxamer 407, 188 and silver sulfadiazine nanoparticles) showed strong antimicrobial activity, while showing low toxicity to fibroblasts.	[^Citation444]
Enhancement of antibacterial activity	Poloxamer 338, poloxamer 407	Bacterial nanocellulose	Below 10 nm	Octenidine	Staphylococcus aureus, Pseudomonas aeruginosa		Bacterial nanocellulose nanoparticles modified with Polysorbate 338 and 407 and encapsulated octenidine exhibited high release antimicrobial activity (release of the octenidine for 8 days), resulting in the antimicrobial activity.	[^Citation445]
Enhancement of antibacterial activity	Cetyltrimethylammonium Bromide, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide	Silver	Below 100 nm		HepG2 cells, Staphylococcus aureus, Escherichia coli, Candida albicans		Single-chain cationic surfactant stabilized the dispersion of silver nanoparticles and increased their antimicrobial properties. Furthermore, the cytotoxicity was predominantly lower than that of the surfactant-only group.	[^Citation446]
Enhancement of antibacterial activity and antioxidative activity	Poloxamer 407	Lipid	121 nm	Turmeric extract	Escherichia coli, Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Streptococcus mutans, Candida fungus		Lipid nanoparticles coated with poloxamer 407 protected the encapsulated turmeric extracts from degradation and improved their antimicrobial and antibacterial activity.	[^Citation447]
Elucidation of the antimicrobial activity mechanism of nanoparticles	Cetyltrimethylammonium bromide, sodium dodecyl sulfate, polyethylene glycol hexadecyl ether	Selenium	20-220 nm		Echinodontium taxodii, seeds of Vigna radiate		Selenium nanoparticles coated with cationic, anionic, and nonionic surfactants differed significantly in their antimicrobial activity and phytotoxicity, respectively. Therefore, surfactants on the surface of the nanoparticles may be involved in the development of various physiological effects.	[^Citation448]
Development of antibacterial biofilm	Curcumin	Selenium	300-400 nm		Staphylococcus aureus, Pseudomonas aeruginosa, L929 cells		Curcumin nanoparticles coated with poloxamer 488 and gelatin (containing silver nanoparticles) showed strong antimicrobial activity, while showing low cytotoxicity to fibroblasts.	[^Citation449]
Improve of shelf life and decontamination of foods	Polysorbate 80	Lipid	78.8 ± 5.3 nm	Citral	Escherichia coli, Staphylococcus aureus, Bacillus cereus, Fungi (Candida albicans)		Citral-loaded solid lipid nanoparticles coated with polysorbate 80 were found to have significantly higher in vitro antimicrobial properties than conventional Citral-loaded emulsions.	[^Citation450]
Improve of shelf life and decontamination of foods	Poloxamer 407	Geraniol	26-412 nm		Salmonella Typhimurium, Escherichia coli O157:H7		The geraniol nanoparticles coated with poloxamer 407 showed a sustained release of geraniol for 24 hours and remained antipathogenic effect for a long period of time. Treatment with these nanoparticles resulted in a reduction of pathogens on the surface of spinach.	[^Citation451]
Water treatment	Polysorbate 80	Silver	50 nm		Gram-positive bacteria, Gram- negative bacteria		Polysorbate 80 coated silver nanoparticles exhibited anti microbial activity for gram-positive and gram- negative bacteria.	[^Citation452]
Water treatment	Cetyltrimethylammonium bromide	Fe3O4	5-10 nm				Fe3O4 nanoparticles coated with cetyltrimethylammonium bromide adsorb antimony on the surface of the nanoparticles, resulting in water purification.	[^Citation453]
Detection of allergens in food	Polysorbate 20	Ovalbumin antibody-coated sensor chips			White and rose wines		Label free SPR based immunoassay for the sensitive detection of ovalbumin in wine was developed by optimizing the analytical conditions (ionic strength and Tween 20 concentration).	[^Citation454]
Active food packaging	Cetyltrimethylammonium bromide	Palladium	Below 25 nm				Poly(3-hydroxybutyrate) films with palladium nanoparticles dispersed in cetyltrimethylammonium bromide were prepared. Prepared films showed oxygen scavenging activity and selective permeability (water vapor and limonene).	[^Citation455]
Oil separation from the corn stillage	Polysorbate 80	Silica	10-20 nm		Condensed corn distillers solubles		A mixture of polysorbate 80 and silica nanoparticles increased the recovery of corn oil from condensed corn distillers solubles by 5-10%.	[^Citation456]

Abbreviations: AUC, area under the curves; Caco-2 cells, human colorectal adenocarcinoma cells; HT-29 cells, human colon cancer cell line; HepG2 cells, human liver cancer cells; Kolliphor HS 15, polyethylene glycol (15)-hydroxystearate; L929 cells, mouse fibroblast-like cells; PLA, poly lactic acid; PLGA, poly(lactic-co-glycolic acid); SDS, sodium dodecyl sulfate; poloxamer, copolymer of polyoxyethylene and polyoxypropylene; polysorbate, polyoxyethylene sorbitan monooleate.

Figure 6 The potential applications of food nanotechnology.

Notes: Data from Martirosyan.²⁶⁵

Figure 7 Illustration of the relationships between diseases, free radicals, reactive oxygen species, and aging in the body, and its regulation by antioxidants from food source.

Notes: Data from Miyazawa²⁴¹ and Adapted from Elsevier Books, 191, Fajardo AM, Bisoffi M, Chapter 18 - Curcumin analogs, oxidative stress, and prostate cancer, 191-202, Copyright 2014, with permission from Elsevier.²⁶⁷.

Figure 8 Age-related decrease in plasma concentrations of antioxidants from food source.

Notes:Data from Mecocci .²⁶⁸

Figure 9 The digestive stages after oral administration and the mechanisms of in vivo uptake of surfactant-coated nanoparticles through the small intestine.

Notes: (A-1) Transcellular route, through the M cells. (A-2) Transcellular route, through the enterocyte. (B) Paracellular route. (C) Persorption route. Data from these published studies ^{318 295 49}

Figure 10 A wide variety of nanoscale materials potentially present in foods from both natural and artificial sources.

Notes: Data from McClements and Xiao.²⁹¹

Figure 11 Overlapping timelines of the development of artificial intelligence and nanomaterials. Since 2010, these two fields have developed a powerful synergy.

Notes: Modified from Singh AV, Rosenkranz D, Ansari MHD, etal Artificial intelligence and machine learning empower advanced biomedical material design to toxicity prediction. Advanced Intelligent Systems. 2020;2:2000084.³⁷⁹

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