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Chandrapala, J. Casein Micelles for Bioactives. Encyclopedia. Available online: (accessed on 07 December 2023).
Chandrapala J. Casein Micelles for Bioactives. Encyclopedia. Available at: Accessed December 07, 2023.
Chandrapala, Jayani. "Casein Micelles for Bioactives" Encyclopedia, (accessed December 07, 2023).
Chandrapala, J.(2021, September 16). Casein Micelles for Bioactives. In Encyclopedia.
Chandrapala, Jayani. "Casein Micelles for Bioactives." Encyclopedia. Web. 16 September, 2021.
Casein Micelles for Bioactives

Caseins and casein micelles are the most prevalent amphiphilic proteins that are widely used to make stabilised emulsions. Caseins can adsorb at the oil–water interface, thus having a high surface activity during homogenisation, processing and storage by preventing coalescence in emulsions under different conditions, such as pH, temperature, structure elasticity and aggregation. Because of these properties, casein is now used to deliver different hydrophobic bioactive in emulsion-based drug delivery systems.

casein micelles encapsulation bioactives microencapsulation nano emulsion hydrogels

1. Introduction

Bioactive food components have received remarkable attention in developing functional foods and nutraceuticals due to their countless physiological health benefits. However, these bioactive components are rapid to inactivation and degradation by light, pH and temperature [1][2]. This rapid degradation can be dodged or slowed down by the encapsulation process till the absorption of these components at the targeted sites. Various encapsulation procedures have been projected to make bioactive components fully functional by preventing their chemical degradation during preparation, storage and transport [3]. There are four delivery systems (lipid-based, carbohydrate-based, hybrid system, protein-based) proposed based on processing conditions, physicochemical stability, sensory and nutritional properties of bioactive components [4][5].

Moreover, the choice of a reasonable protein for a specific transporter relies on the properties of the particle (e.g., size, charge, surface qualities and biodegradability), properties of the bioactive compound to be encapsulated (e.g., polarity, solubility and stability), and environmental conditions (e.g., pH, ionic quality, solvent properties and temperature) [6]. Though various proteins have been widely used as delivery vehicles, milk proteins (caseins and whey) are exotic encapsulation particles due to their elastic structural and functional properties. They have efficient bioactive binding abilities, better encapsulation efficiencies and controlled and target release of bioactive components [3]. As compared to whey proteins, casein micelles are recognised as a natural vehicle for bioactive components since casein proteins have a porous structure with cavities and are recognised as GRAS (Generally Recognized as Safe) [7]. Casein micelles have unique structural and physicochemical properties, such as binding with ions and small molecules to form macromolecules, exceptional stabilising characteristics, self-assembling, emulsifying and water-binding abilities. The porous structure and unique functional properties make them appropriate for the transport of bioactive components; therefore, they have been used in traditional and new drug delivery systems [8].

Furthermore, casein micelles are amphiphilic, which then can act as a nano-vehicle for both hydrophobic bioactive components such as vitamin (D 2, D 3, E, K) and/or hydrophilic macromolecules such as whey protein and polysaccharides. The vulnerability of caseins to proteolysis [9] guarantees the high discharge of bioactives by a proteolytic enzyme in the gastric tract. The cellular uptake investigation of casein micelles revealed that casein spheres could enter the plasma layer in an independent energy fashion due to the proline-rich peptide sequence in casein [10]. Moreover, caseins have various preservation capabilities essential for the safety of sensitive encapsulated bioactive components, thereby controlling these bioactive agents’ biosafety and bioavailability. The casein spheres could significantly advance as one of the best nutraceuticals and drug delivery systems due to its protein matrix rich in surface reactive groups, hollow structure and innovative cell-penetrating properties [8][11].

Although much work has been done regarding caseins as a delivery system for pharmaceuticals, functional foods and nutraceuticals [12][13][14][15], still some areas such as induced structural modification of casein micelles, by altering secondary processing parameters, need to be explored. A recent review by Nascimento and colleagues [16] presented an overview of casein-based hydrogels. Ranadheera [17] examined casein and casein micelles’ unique properties as capsules, emulsions, hydrogels and film coatings and observed that different processing parameters can alter casein micelles’ techno-functionalities, consequently facilitating the encapsulation of food bioactive components inside casein micelles by binding at its hydrophobic and hydrophilic domains. Thus, this review provides updated and most recent studies about casein micelle as a delivery vehicle with particular attention to deliver bioactives in functional foods and nutraceuticals, along with detailed facts on how pH and temperature affect the incorporated food bioactive component’s binding and release properties.

2. Casein Micelles and Its Structure

Another characteristic of caseins is the proline residues, specifically in β caseins, which disrupt the casein micelle structure and give a non-globular nature to caseins with an open structure. These proline-rich caseins carry numerous properties like resistance to heat denaturation, favouring the elastic conformations in solution, great structural flexibility against environmental stresses, specific proteolytic cleavage and targeted drug delivery [18].

Numerous studies have been undertaken on how caseins interact with each other in the past. In 1920, it was considered that caseins undergo self-association as well as with other caseins. The association of caseins within a micelle depends on pH, ionic strength and temperature [19]. Von and Waugh [20] were the first to perform a thorough study about caseins interactions and the complexes they may form when calcium concentrations, temperature and pH are varied [20]. However, there have been several divergent opinions and debates about the critical forms of relationships that dictate casein structure [18].

Hydrophobic interactions occur when two opposing surfaces come close together by the exclusion of water. Only the interactions of β caseins with other caseins are typically hydrophobic, which results in β casein dissociation from casein micelles when hydrophobic interactions are minimised in milk upon cooling [21]. Typically, when β casein is cooled, up to 30% of it dissociates from the casein micelles, while the remainder remains attached to the micelles. However, when milk is heated at 30 °C, all dissociated β caseins reassociate with the micelles. This happens to β caseins associated with other caseins rather than attaching to calcium phosphate nanoclusters [22]. Although certain β caseins will dissociate from the casein micelle, this does not seem to disrupt the casein micelles structure. As other caseins do not form hydrophobic interaction, so there is no dissociation upon cooling. According to amino acid concentrations, 28% of κ casein, 30% of α s2 casein, 32% of α s1 casein and 34% of β casein residues are hydrophobic, or about 1 in 3 [23][24]. Hydrophobic Clustering Analysis (HCA) was carried out by Horne, 2017 to explore the hydrophobic residues along the caseins sequence. The sole purpose of 2D-HCA was to show that all caseins contain segments that might interact hydrophobically with other caseins [18].

Several models of casein micelles have been reported based on the characteristics and interactions of caseins. The oldest model was the core coat model proposed by Waugh, 1958 as in Figure 1 a. According to this model, casein micelles composed of variable-sized cores of insoluble slats of α or β casein covered by a coat of κ caseins [25]. Later, a submicelle model was projected by Schmidt, 1982 shown in Figure 1 b, which suggested that casein micelles were distinct subunits composed of colloidal calcium phosphate crosslinkages [26]. Walstra in 1984 proposed a submicelle model according to which casein micelles are the assembly of roughly spherical subunits or submicelles held together by hydrophobic interactions and calcium phosphate bridges [27].

Figure 1. Casein micelles model by Waugh 1958 (a), models by Schmidt in 1982 (b), model proposed by Walstra in 1990 (c1) & 1999 (c2), (differs in calcium phosphate location), Dual binding model by Horne (2003) (d1) and interpretation of Schmidt’s model in 2005 (d2).

3. Factors Affecting Techno-Functionalities of Casein Micelles

After discussing the numerous mechanisms by which caseins interact during micelle formation, it is important to explore how such interactions can be engineered to change the functional properties of casein micelles. The structures and techno-functionalities of casein micelles could be modified by various intrinsic and extrinsic factors as shown in Table 1 . However, this review will focus just on temperature and pH effects.

Table 1. Intrinsic and Extrinsic Factors to Modify Casein Micelles Structure and Functionalities.
Physical Methods Biochemical Effect Charge on Casein Chemical Methods Biochemical Effect Charge on Casein Enzymatic Methods Biochemical Effect Charge on Casein
Temperature (High)
Temperature (Low)
Blockage of lysyl residues by lactose
β-lactoglobulin covalent
Calcium phosphate precipitation and solubilisation
Β casein solubilisation
Reduced negative charge
Not determined
Reaction with sugar Glycation
Blockage of lysyl residues
Blockage of lysyl residues
More negative
More negative
organic phosphate removal from phosphoseryl residues Reduced negativity
pH (Acid)
pH (alkaline)
Protonation of casein
Decrease of cations casein interactions
Increase of the casein ionisation
Insolubilisation of calcium phosphate
Reduced negativity
More negative
Chemical Reticulation
Blockage of lysyl residues More negative Deamidation
- Release of ammonia from glutamine transformed into glutamic residues More negative
Casein micelles distruptions Not determined Phosphorylation
Lysyl and glutamine crosslinking Enhanced negativity
Casein micelles disruptions Not determined Glycosylation     Deglycosylation
- Release of NANA No effect
Addition of cations (di & trivalent)
Direct association of added cation to casein
Association of cation-inorganic phosphate to casein micelles
Increase in ionic strength
Less negative Succinylation
Lysyl residues inhibition More negative
More negative
- Release of caseino macropeptide negatively charged between 106 to 169 peptides Reduced negativity between 1–105 peptides
Adding salt
Micellar calcium solubilisation Ionic strength enhancement No change            
Removal of diffusible ions Diffusible ions removal More negative ions            
Calcium chelatants addition
Casein and calcium association reductions
Micellar calcium phosphate solubilisation
More negative ions            
External ligands addition
Hydrophobic and hydrogen interactions to caseins ND          

The heating of proteins induces conformational changes, exposing the hydrophobic sites. Owing to the absence of a tertiary structure, casein micelles are heat stable. However, distinct changes have been noted concerning the frequency of the heat. Several biochemical modifications are identified, including deamidation of asparagine and glutamine residues, proteolysis [29], and reticulation between amino acids, which results in protein polymerisation, disulphide bridge breakdown and exchange of free thiols on cysteine residues. During heat treatment, the mineral fraction, especially calcium phosphate, becomes less soluble in the aqueous phase, which may interact with casein micelles [70]. When the temperature is less than 95 °C for a few minutes, the changes in salt equilibria are reversible. In comparison, prolonged exposure to high temperatures (for example, 120 °C for 20 min) results in irreversible alterations to the casein micelles and salt distribution. Casein phosphoseryl residues may be partly hydrolysed at temperatures greater than 110 °C [30]. There are limited and old dated reports describing the physicochemical changes in casein micelles induced by cooling.

Koutina and colleagues [31] reported that calcium and phosphorus concentrations in the soluble phase were more significant at 4 °C than at 40 °C due to the increased solubility of calcium phosphate at lower temperatures. Simultaneously, reduced hydration of casein micelles and release of β casein from the micellar structure has been observed [22]. Indeed, temperature reduction alters protein interactions, which allows the transfer of β casein into the aqueous system. These modifications are reversible, and the prior clustering may be restored after heating; however, the native framework is not fully restored because β casein would not revert to its original location [32]. Liu and colleagues [32] confirmed that the volume of soluble casein, hydration and apparent voluminosity of casein micelles reduced as the temperature increased demonstrating that casein micelles structure and mineral in milk were temperature-dependent between 10 °C and 40 °C. However, the mineral system reaction is prompt during this heating, while casein micelle re-equilibration occurs gradually during cooling. This method could be opted to obtain purified β casein and obtain remained novel casein micelles (less mineralised, depleted in β casein and more hydrated) with innovative techno-functionalities [71].

At pH 5.6, casein micelles enlarge and dissociation of caseins approaches a plateau, with β casein dissociation reaching a maximum [39]. A new limited group of caseins similar to casein aggregates is found in this pH spectrum of 5.6 to 6 [40]. These smaller units range in diameter from about 20 to 35 nm and have a molecular weight of 106 and 107 g·mol −1 . As the pH value decreases (6.7, 6.4, 6.1, 5.8, 5.5), the proportion of these smaller particles increases. The non-dissociated casein micelles seemed to be close to native casein micelles in size, hydration, appearance and zeta potential [40]. Demineralisation of casein micelles by reducing the pH from 6.7 to 5.2 resulted in a reduction of micelles’ granularity as determined by cryo-transmission electron microscopy, atomic force microscopy [72], and by the presence of a distinctive point of inflection in SAXS profiles [73]. At pH 4.6, caseins have no charge and therefore have negligible solubility and got precipitate. Acidification causes a similar degree of micellar destruction regardless of the type of acid used (lactic, citric), as physicochemical modifications primarily depend upon pH. However, the composition of the aqueous phase, especially its ionic state, varies according to the acid form, which has an impact on the structure and functionality of acidified caseins [74].

4. Casein Micelles–Based Delivery Systems

The scientific community has spent many decades attempting to characterise and comprehend the complexity of casein micelles in terms of composition, structure and functional properties. As discussed in the previous section, casein micelles may be modified under various temperature and pH conditions to alter their techno functionalities. However, other physical, chemical or enzymatic methods have also been used to alter the technological functionalities of casein micelles and these innovative micellar functionalities have been utilised in various functional foods and nutraceuticals as carriers for bioactive compounds. The bioactive’s low absorption and efficacy are associated with deprived bioavailability upon taking through the oral route and their vulnerability to degradation (chemical, physical and enzymatic) during different processing, storage and transportation. These factors require the protection of these bioactive. In this context, casein micelles were exploited to form microparticles, nanoparticles and hydrogels for targeted delivery of bioactive food compounds at the site of action, as illustrated in Table 2 [75][76][77][78][79].

Table 2. Casein Micelles-Based Capsules and Hydrogels in Delivering Food Bioactives.

Casein Type The Technique Used for Preparing Loaded Reassembled Casein Micelles Bioactive Encapsulation Mechanism References
Micellar casein • Casein–emodin complex formation by vortex
• Heat and Ultrasound treatments
• Spray-drying microencapsulation
• In Vitro digestion evaluation
Emodin Microencapsulation [80]
β casein micelle • Drug loaded β caseins dispersion
• Freeze drying
• Making and description of gastro-resistant Nanoparticle in Microparticle Delivery Systems
• pH 2 and 6.5
• In Vitro drug release
Antiretroviral (ARV) combinations of Darunavir, efavirenz and ritonavir encapsulation in β caseins and further within Eudragit L100 Co-encapsulation,
Nanoparticle-in-microparticle delivery system (NiMDS)
Casein gels • Casein gel production at pH 1 and 9
• Spray-dried gel and tablet
• Oven-dried gel and tablets
• Controlled release under various compression methods
Caffeine Gels [82][83]
β casein micelle
Sodium Caseinate
• β casein preparation in 7.4 phosphate buffer
• Blending of protein and resveratrol
• Production of polysaccharide conjugates by Millard reaction
Resveratrol loading at pH 7.5
Resveratrol Encapsulation
β casein depleted Casein micelles • Centrifugation
• Lyophilisation
• Mixing by shaker
• Ultracentrifugation
• Enzymatic crosslinking
Linoleic acid Nanoencapsulation [87]
Caseins • Acidification
• Homogenisation at high pressure
• Curcumin/casein/soy polysaccharide complex at pH 10.0
• In Vitro digestion evaluation
• CUR pharmacokinetics of CUR/CN/SSPS in mice
Curcumin Nanoencapsulation [88]
Casein Micelle • Chemical acidification
• Crosslinking by transglutaminase
Jaboticaba extract Hydrogels [14]
Sodium casienate/Carrageenan • Primary and multilayered emulsion preparations
• Microbeads preparation by gelation in an atomiser
β carotene Emulsions/Gels [89]
Casein micelles • Mineral arrangement restoration and spray-drying
• Homogenisation at high pressure
• pH and temperature-induced opening
β carotene Nanoencapsulation [11][90][91][92]
Re-assembled casein micelles (r-CM)
Sodium caseinate (CNP)
• Binding at pH 7.4 and temperature 74 °C
• Centrifugation
• EGGC binding r-CM and CNP
• Encapsulation efficiency determination
Epigallocatechin gallate (EGGC), folic acid Nanoencapsulation [93]
Casein micelles • Preparation of casein-PAAm hydrogels by free radical polymerisation Polyacrylamide Hydrogels [94]
Casein micelles • Spray-drying pH-shifting
• High-pressure treatment
curcumin Nanoencapsulation [95][96][97][98][99][100]
Reassembled Casein micelles • Restoration of mineral composition and ultrahigh-pressure homogenisation Vitamin D3 Nanoencapsulation [91][92][101][102][103]
Micellar Casein • A shift in pH and ultrasonication Fish oil Emulsions [104]
Micellar casei
Re-assembled casein micelle from micellar casein
• A shift in pH and ultrasonication Vegetable oil
(Lactobacillus and Bifidobacteria
Casein micelles • Mineral composition restoration
• Homogenisation with high pressure
Omega-3 Nanoencapsulation [104]
β Casein micelles • Lyophilization Celecoxib Nanoencapsulation [106]
Casein micelles + konjac glucomannan (KGM) • Enzyme-induced casein KGM hydrogels preparation
• Ageing in refrigeration
Docetaxel Gel [107]
Casein micelles • Skim milk natural conditions
• Thermally treated commercial skim milk
Vitamin A Nanoencapsulation [102][108]
Casein micelles • Mineral composition restoration and homogenisation at high pressure
• Re-assembly of casein micelles
Vitamin D2 Nanoencapsulation [101]
Casein micelles   Rosemary Extract Nanoencapsulation [109]
Casein micelle   Lactoferrin Nanoencapsulation [110]
Casein micelle • Spray-drying crosslinked with genipin Alfuzosin suspension [111]
Casein micelle • Spray-drying crosslinked with genipin Flutamide Microencapsulation [111]

In the nutraceuticals industry, both the hydrophobic and hydrophilic properties of casein micelles have been exploited [112]. The hydrophobic molecules present several bonding options when binding to the caseins, for example, hydrogen bonding, van der Waals forces and hydrophobic interactions [9]. A hydrophobic molecule of vitamin D 2 has been encapsulated by Semo and colleagues [8], within casein micelle by using sodium caseinate. However, the pH of the solution was changed to 6.7 according to natural milk pH. Caseins were able to encapsulate vitamin D 2 efficiently due to hydrophobic domains and self-assembled micelle structure. Moreover, vitamin D 2 was found 5.5 times more in casein micelles than in serum.

It has also been stated that casein interactions with polyphenols alter the conformation of caseins, resulting in a decrease in the number of α helices and β sheets [113], so in a casein –polyphenol mixture, the antioxidant activity decreased slightly, indicating a major influence of casein on polyphenol activity. This reduction was more evident in casein that had been incubated with catechin or epicatechin. However, MALDI-TOF mass spectra of incubated caseins did not reveal any stable adduct between the individual caseins, neither with catechin/epicatechin nor with cocoa polyphenols derived from cocoa [113].

All these findings offered help for future utilisation of casein micelles to make complexes with other polysaccharides/lutein/resveratrol to enhance their emulsifying and stabilising properties to acts as a carrier for polyphenols.


  1. Gleeson, J.P.; Ryan, S.M.; Brayden, D. Oral delivery strategies for nutraceuticals: Delivery vehicles and absorption enhancers. Trends Food Sci. Technol. 2016, 53, 90–101.
  2. Oh, Y.S. Bioactive compounds and their neuroprotective effects in diabetic complications. Nutrients 2016, 8, 472.
  3. Santiago, L.G.; Castro, G.R. Novel technologies for the encapsulation of bioactive food compounds. Curr. Opin. Food Sci. 2016, 7, 78–85.
  4. De Vos, P.; Faas, M.M.; Spasojevic, M.; Sikkema, J. Encapsulation for preservation of functionality and targeted delivery of bioactive food components. Int. Dairy J. 2010, 20, 292–302.
  5. Benshitrit, R.C.; Levi, C.S.; Tal, S.L.; Shimoni, E.; Lesmes, U. Development of oral food-grade delivery systems: Current knowledge and future challenges. Food Funct. 2012, 3, 10–21.
  6. Martins, J.T.; Bourbon, A.I.; Pinheiro, A.C.; Fasolin, L.H.; Vicente, A.A. Protein-based structures for food applications: From macro to nanoscale. Front. Sustain. Food Syst. 2018, 2, 77.
  7. Rehan, F.; Ahemad, N.; Gupta, M. Casein nanomicelle as an emerging biomaterial—A comprehensive review. Colloids Surf. B Biointerfaces 2019, 179, 280–292.
  8. Semo, E.; Kesselman, E.; Danino, D.; Livney, Y. Casein micelle as a natural nano-capsular vehicle for nutraceuticals. Food Hydrocoll. 2007, 21, 936–942.
  9. Livney, Y.D. Milk proteins as vehicles for bioactives. Curr. Opin. Colloid Interface Sci. 2010, 15, 73–83.
  10. Liu, C.; Yao, W.; Zhang, L.; Qian, H.; Wu, W.; Jiang, X. Cell-penetrating hollow spheres based on milk protein. Chem. Commun. 2010, 46, 7566–7568.
  11. Głąb, T.K.; Boratyński, J. Potential of Casein as a Carrier for Biologically Active Agents. Top. Curr. Chem. 2017, 375, 71.
  12. Cohen, Y.; Ish-Shalom, S.; Segal, E.; Nudelman, O.; Shpigelman, A.; Livney, Y.D. The bioavailability of vitamin D3, a model hydrophobic nutraceutical, in casein micelles, as model protein nanoparticles: Human clinical trial results. J. Funct. Foods 2017, 30, 321–325.
  13. Ghayour, N.; Hosseini, S.M.H.; Eskandari, M.H.; Esteghlal, S.; Nekoei, A.-R.; Hashemi Gahruie, H.; Tatar, M.; Naghibalhossaini, F. Nanoencapsulation of quercetin and curcumin in casein-based delivery systems. Food Hydrocoll. 2019, 87, 394–403.
  14. Nascimento, L.G.L.; Casanova, F.; Silva, N.F.N.; Teixeira, Á.V.N.d.C.; Júnior, P.P.d.S.P.; Vidigal, M.C.T.R.; Stringheta, P.C.; Carvalho, A.F. Use of a crosslinked casein micelle hydrogel as a carrier for jaboticaba (Myrciaria cauliflora) extract. Food Hydrocoll. 2020, 106, 105872.
  15. Marreto, R.N.; Ramos, M.F.S.; Silva, E.J.; de Freitas, O.; de Freitas, L.A.P. Impact of Cross-linking and Drying Method on Drug Delivery Performance of Casein–Pectin Microparticles. AAPS PharmSciTech 2013, 14, 1227–1235.
  16. Nascimento, L.G.L.; Casanova, F.; Silva, N.F.N.; Teixeira, A.V.N.C.; Carvalho, A.F. Casein-based hydrogels: A mini-review. Food Chem. 2020, 314, 126063.
  17. Ranadheera, C.; Liyanaarachchi, W.; Chandrapala, J.; Dissanayake, M.; Vasiljevic, T. Utilizing unique properties of caseins and the casein micelle for delivery of sensitive food ingredients and bioactives. Trends Food Sci. Technol. 2016, 57, 178–187.
  18. Horne, D.S. A balanced view of casein interactions. Curr. Opin. Colloid Interface Sci. 2017, 28, 74–86.
  19. Schmidt, D.G. Differences between the association of the genetic variants B, C and D of αs1-casein. Biochim. Biophys. Acta Protein 1970, 221, 140–142.
  20. Von Hippel, P.H.; Waugh, D.F. Casein: Monomers and Polymers1. J. Am. Chem. Soc. 1955, 77, 4311–4319.
  21. Creamer, L.; Berry, G.; Mills, O. A study of the dissociation of b-casein from the bovine casein micelle at low temperature [milk and cream]. N. Z. J. Dairy Sci. Technol. 1977, 12, 58–66.
  22. Bigelow, C.C. On the average hydrophobicity of proteins and the relation between it and protein structure. J. Theor. Biol. 1967, 16, 187–211.
  23. Swaisgood, H.E.; Timasheff, S.N. Association of αs-casein C in the alkaline pH range. Arch. Biochem. Biophys. 1968, 125, 344–361.
  24. Arunachalam, J.; Gautham, N. Hydrophobic clusters in protein structures. Proteins 2008, 71, 2012–2202.
  25. Waugh, D.F. The interactions of αs-β- and κ-caseins in micelle formation. Discuss. Faraday Soc. 1958, 25, 186–192.
  26. Horne, D.S. Casein structure, self-assembly and gelation. Curr. Opin. Colloid Interface Sci. 2002, 7, 456–461.
  27. Walstra, P. Casein sub-micelles: Do they exist? Int. Dairy J. 1999, 9, 189–192.
  28. Dalgleish, D.G.; Corredig, M. The Structure of the Casein Micelle of Milk and Its Changes During Processing. Annu. Rev. Food Sci. Technol. 2012, 3, 449–467.
  29. Gaucheron, F.; MollÉ, D.; Pannetier, R. Influence of pH on the heat-induced proteolysis of casein molecules. J. Dairy Res. 2001, 68, 71–80.
  30. Van Boekel, M.A.J.S. Heat-induced deamidation, dephosphorylation and breakdown of caseinate. Int. Dairy J. 1999, 9, 237–241.
  31. Koutina, G.; Knudsen, J.C.; Andersen, U.; Skibsted, L.H. Temperature effect on calcium and phosphorus equilibria in relation to gel formation during acidification of skim milk. Int. Dairy J. 2014, 36, 65–73.
  32. Liu, D.Z.; Weeks, M.G.; Dunstan, D.E.; Martin, G.J.O. Temperature-dependent dynamics of bovine casein micelles in the range 10–40 °C. Food Chem. 2013, 141, 4081–4086.
  33. Corzo-Martínez, M.; Moreno, F.J.; Villamiel, M.; Harte, F.M. Characterization and improvement of rheological properties of sodium caseinate glycated with galactose, lactose and dextran. Food Hydrocoll. 2010, 24, 88–97.
  34. Bhatt, H.; Cucheval, A.; Coker, C.; Patel, H.; Carr, A.; Bennett, R. Effect of lactosylation on plasmin-induced hydrolysis of β-casein. Int. Dairy J. 2014, 38, 213–218.
  35. McCarthy, N.A.; Kelly, A.L.; O’Mahony, J.A.; Fenelon, M.A. The physical characteristics and emulsification properties of partially dephosphorylated bovine β-casein. Food Chem. 2013, 138, 1304–1311.
  36. Tezcucano Molina, A.C.; Alli, I.; Konishi, Y.; Kermasha, S. Effect of dephosphorylation on bovine casein. Food Chem. 2007, 101, 1263–1271.
  37. De Kruif, C.G. Skim Milk Acidification. J. Colloid Interface Sci. 1997, 185, 19–25.
  38. McMahon, D.J.; Du, H.; McManus, W.R.; Larsen, K.M. Microstructural changes in casein supramolecules during acidification of skim milk. J. Dairy Sci. 2010, 93, 1783.
  39. Dalgleish, D.G.; Law, A.J.R. pH-Induced dissociation of bovine casein micelles. II. Mineral solubilization and its relation to casein release. J. Dairy Res. 1989, 56, 727–735.
  40. Silva, N.N.; Piot, M.; de Carvalho, A.F.; Violleau, F.; Fameau, A.-L.; Gaucheron, F. pH-induced demineralization of casein micelles modifies their physico-chemical and foaming properties. Food Hydrocoll. 2013, 32, 322–330.
  41. Ahmad, S.; Piot, M.; Rousseau, F.; Grongnet, J.F.; Gaucheron, F. Physico-chemical changes in casein micelles of buffalo and cow milks as a function of alkalinisation. Dairy Sci. Technol. 2009, 89, 387–403.
  42. Huppertz, T.; Vaia, B.; Smiddy, M.A. Reformation of casein particles from alkaline-disrupted casein micelles. J. Dairy Res. 2008, 75, 44–47.
  43. Silva, N.F.N.; Saint-Jalmes, A.; de Carvalho, A.F.; Gaucheron, F. Development of Casein Microgels from Cross-Linking of Casein Micelles by Genipin. Langmuir 2014, 30, 10167–10175.
  44. Yang, M.; Shi, Y.; Wang, P.; Liu, H.; Wen, P.; Ren, F. Effect of succinylation on the functional properties of yak caseins: A comparison with cow caseins. Dairy Sci. Technol. 2014, 94, 359–372.
  45. Miwa, N.; Yokoyama, K.; Wakabayashi, H.; Nio, N. Effect of deamidation by protein-glutaminase on physicochemical and functional properties of skim milk. Int. Dairy J. 2010, 20, 393–399.
  46. Miwa, N.; Nio, N.; Sonomoto, K. Effect of enzymatic deamidation by protein-glutaminase on the textural and microstructural properties of set yoghurt. Int. Dairy J. 2014, 36, 1–5.
  47. Huppertz, T.; de Kruif, C.G. Disruption and reassociation of casein micelles during high pressure treatment: Influence of whey proteins. J. Dairy Res. 2007, 74, 194–197.
  48. Huppertz, T.; Fox, P.F.; Kelly, A.L. High pressure treatment of bovine milk: Effects on casein micelles and whey proteins. J. Dairy Res. 2004, 71, 97–106.
  49. Menéndez-Aguirre, O.; Kessler, A.; Stuetz, W.; Grune, T.; Weiss, J.; Hinrichs, J. Increased loading of vitamin D 2 in reassembled casein micelles with temperature-modulated high pressure treatment. Food Res. Int. 2014, 64, 74–80.
  50. Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J. High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles. High Press. Res. 2011, 31, 265–274.
  51. Medina, A.L.; Colas, B.; Le Meste, M.; Renaudet, I.; Lorient, D. Physicochemical and dynamic properties of caseins modified by chemical phosphorylation. J. Food Sci. 1992, 57, 617–621.
  52. Moon, J.-H.; Hong, Y.-H.; Huppertz, T.; Fox, P.F.; Kelly, A.L. Properties of casein micelles cross-linked by transglutaminase. Int. J. Dairy Technol. 2009, 62, 27–32.
  53. Huppertz, T.; de Kruif, C.G. Structure and stability of nanogel particles prepared by internal cross-linking of casein micelles. Int. Dairy J. 2008, 18, 556–565.
  54. Liu, Z.; Juliano, P.; Williams, R.P.W.; Niere, J.; Augustin, M.A. Ultrasound effects on the assembly of casein micelles in reconstituted skim milk. J. Dairy Res. 2014, 81, 146–155.
  55. Madadlou, A.; Mousavi, M.E.; Emam-djomeh, Z.; Ehsani, M.; Sheehan, D. Sonodisruption of re-assembled casein micelles at different pH values. Ultrason. Sonochem. 2009, 16, 644–648.
  56. Madadlou, A.; Emam-Djomeh, Z.; Mousavi, M.E.; Mohamadifar, M.; Ehsani, M. Acid-induced gelation behavior of sonicated casein solutions. Ultrason. Sonochem. 2010, 17, 153–158.
  57. Zheng, L.I.U.; Juliano, P.; Williams, R.P.W.; Niere, J.; Augustin, M.A. Ultrasound improves the renneting properties of milk. Ultrason. Sonochem. 2014, 21, 2131–2137.
  58. Cases, E.; Vidal, V.; Cuq, J.L. Effect of K-Casein Deglycosylation on the Acid Coagulability of Milk. J. Food Sci. 2003, 68, 2406–2410.
  59. Jacobsen, J.; Wind, S.L.; Rasholt, E.L.; van den Brink, J.M. N-Glycosidase F improves gel firmness in fermented milk products. Int. Dairy J. 2014, 38, 169–173.
  60. Mekmene, O.; Le Graët, Y.; Gaucheron, F. Theoretical Model for Calculating Ionic Equilibria in Milk as a Function of pH: Comparison to Experiment. J. Agric. Food Chem. 2010, 58, 4440–4447.
  61. Omoarukhe, E.D.; On-Nom, N.; Grandison, A.S.; Lewis, M.J. Effects of different calcium salts on properties of milk related to heat stability. Int. J. Dairy Technol. 2010, 63, 504–511.
  62. Vidal, V.; Marchesseau, S.; Cuq, J.L. Physicochemical Properties of Acylated Casein Micelles in Milk. J. Food Sci. 2002, 67, 42–47.
  63. Wang, J.; Su, Y.; Jia, F.; Jin, H. Characterization of casein hydrolysates derived from enzymatic hydrolysis. Chem. Cent. J. 2013, 7, 62.
  64. Luo, Y.; Pan, K.; Zhong, Q. Physical, chemical and biochemical properties of casein hydrolyzed by three proteases: Partial characterizations. Food Chem. 2014, 155, 146–154.
  65. Huppertz, T.; Fox, P.F. Effect of NaCl on some physico-chemical properties of concentrated bovine milk. Int. Dairy J. 2006, 16, 1142–1148.
  66. Hussain, R.; Gaiani, C.; Aberkane, L.; Scher, J. Characterization of high-milk-protein powders upon rehydration under various salt concentrations. J. Dairy Sci. 2011, 94, 14–23.
  67. De Kort, E.; Minor, M.; Snoeren, T.; van Hooijdonk, T.; van der Linden, E. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions. Int. Dairy J. 2011, 21, 907–913.
  68. Schokker, E.P.; Church, J.S.; Mata, J.P.; Gilbert, E.P.; Puvanenthiran, A.; Udabage, P. Reconstitution properties of micellar casein powder: Effects of composition and storage. Int. Dairy J. 2011, 21, 877–886.
  69. Haratifar, S.; Corredig, M. Interactions between tea catechins and casein micelles and their impact on renneting functionality. Food Chem. 2014, 143, 27–32.
  70. Davies, D.T.; White, J.C.D. The use of ultrafiltration and dialysis in isolating the aqueous phase of milk and in determining the partition of milk constituents between the aqueous and disperse phases. J. Dairy Res. 1960, 27, 171–190.
  71. Van Hekken, D.L.; Holsinger, V.H. Use of cold microfiltration to produce unique β-casein enriched milk gels. Le Lait 2000, 80, 69–76.
  72. Ouanezar, M.; Guyomarc’h, F.; Bouchoux, A. AFM Imaging of Milk Casein Micelles: Evidence for Structural Rearrangement upon Acidification. Langmuir 2012, 28, 4915–4919.
  73. Marchin, S.; Putaux, J.-L.; Pignon, F.; Leonil, J. Effects of the environmental factors on the casein micelle structure studied by Cryo transmission microscopy and small-angle X-ray scattering/ultrasmall-angle X-ray scattering. J. Chem. Phys. 2007, 126, 045101.
  74. Broyard, C.; Gaucheron, F. Modifications of structures and functions of caseins: A scientific and technological challenge. Dairy Sci. Technol. 2015, 95, 831–862.
  75. Shapira, A.; Assaraf, Y.G.; Livney, Y.D. Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs. Nanomed. Nanotechnol. Biol. Med. 2010, 6, 119–126.
  76. De Kruif, C.; Anema, S.G.; Zhu, C.; Havea, P.; Coker, C. Water holding capacity and swelling of casein hydrogels. Food Hydrocoll. 2015, 44, 372–379.
  77. Song, F.; Zhang, L.-M.; Shi, J.-F.; Li, N.-N. Novel casein hydrogels: Formation, structure and controlled drug release. Colloids Surf. B Biointerfaces 2010, 79, 142–148.
  78. Bonnaillie, L.; Zhang, H.; Akkurt, S.; Yam, K.; Tomasula, P. Casein Films: The Effects of Formulation, Environmental Conditions and the Addition of Citric Pectin on the Structure and Mechanical Properties. Polymers 2014, 6, 2018–2036.
  79. Lesmes, U.; Sandra, S.; Decker, E.A.; McClements, D.J. Impact of surface deposition of lactoferrin on physical and chemical stability of omega-3 rich lipid droplets stabilised by caseinate. Food Chem. 2010, 123, 99–106.
  80. Yang, M.; Wei, Y.; Ashokkumar, M.; Qin, J.; Han, N.; Wang, Y. Effect of ultrasound on binding interaction between emodin and micellar casein and its microencapsulation at various temperatures. Ultrason. Sonochem. 2020, 62, 104861.
  81. Singh Chauhan, P.; Abutbul Ionita, I.; Moshe Halamish, H.; Sosnik, A.; Danino, D. Multidomain drug delivery systems of β-casein micelles for the local oral co-administration of antiretroviral combinations. J. Colloid Interface Sci. 2021, 592, 156–166.
  82. Tan, S.; Ebrahimi, A.; Langrish, T. Controlled release of caffeine from tablets of spray-dried casein gels. Food Hydrocoll. 2019, 88, 13–20.
  83. Tan, S.; Ebrahimi, A.; Langrish, T. Smart release-control of microencapsulated ingredients from milk protein tablets using spray drying and heating. Food Hydrocoll. 2019, 92, 181–188.
  84. Cheng, H.; Dong, H.; Liang, L. A comparison of β-casein complexes and micelles as vehicles for trans-/cis-resveratrol. Food Chem. 2020, 330, 127209.
  85. Consoli, L.; Dias, R.A.; Rabelo, R.S.; Furtado, G.F.; Sussulini, A.; Cunha, R.L.; Hubinger, M.D. Sodium caseinate-corn starch hydrolysates conjugates obtained through the Maillard reaction as stabilizing agents in resveratrol-loaded emulsions. Food Hydrocoll. 2018, 84, 458–472.
  86. Gorji, E.G.; Rocchi, E.; Schleining, G.; Bender-Bojalil, D.; Furtmüller, P.G.; Piazza, L.; Iturri, J.J.; Toca-Herrera, J.L. Characterization of resveratrol–milk protein interaction. J. Food Eng. 2015, 167, 217–225.
  87. Duerasch, A.; Herrmann, P.; Hogh, K.; Henle, T. Study on β-Casein Depleted Casein Micelles: Micellar Stability, Enzymatic Cross-Linking, and Suitability as Nanocarriers. J. Agric. Food Chem. 2020, 68, 13940–13949.
  88. Xu, G.; Li, L.; Bao, X.; Yao, P. Curcumin, casein and soy polysaccharide ternary complex nanoparticles for enhanced dispersibility, stability and oral bioavailability of curcumin. Food Biosci. 2020, 35, 100569.
  89. Perrechil, F.A.; Maximo, G.J.; Sato, A.C.K.; Cunha, R.L. Microbeads of Sodium Caseinate and κ-Carrageenan as a β-Carotene Carrier in Aqueous Systems. Food Bioprocess Technol. 2020, 13, 661–669.
  90. Yi, J.; Lam, T.I.; Yokoyama, W.; Cheng, L.W.; Zhong, F. Beta-carotene encapsulated in food protein nanoparticles reduces peroxyl radical oxidation in Caco-2 cells. Food Hydrocoll. 2015, 43, 31–40.
  91. Haham, M.; Ish-Shalom, S.; Nodelman, M.; Duek, I.; Segal, E.; Kustanovich, M.; Livney, Y.D. Stability and bioavailability of vitamin D nanoencapsulated in casein micelles. Food Funct. 2012, 3, 737–744.
  92. Levinson, Y.; Ish-Shalom, S.; Segal, E.; Livney, Y.D. Bioavailability, rheology and sensory evaluation of fat-free yogurt enriched with VD3 encapsulated in re-assembled casein micelles. Food Funct. 2016, 7, 1477.
  93. Malekhosseini, P.; Alami, M.; Khomeiri, M.; Esteghlal, S.; Nekoei, A.R.; Hosseini, S.M.H. Development of casein-based nanoencapsulation systems for delivery of epigallocatechin gallate and folic acid. Food Sci. Nutr. 2019, 7, 519–527.
  94. Ma, J.; Lee, J.; Han, S.S.; Oh, K.H.; Nam, K.T.; Sun, J.-Y. Highly Stretchable and Notch-Insensitive Hydrogel Based on Polyacrylamide and Milk Protein. ACS Appl. Mater. Interfaces 2016, 8, 29220–29226.
  95. Sahu, A.; Kasoju, N.; Bora, U. Fluorescence study of the curcumin–casein micelle complexation and its application as a drug nanocarrier to cancer cells. Biomacromolecules 2008, 9, 2905–2912.
  96. Rahimi Yazdi, S.; Corredig, M. Heating of milk alters the binding of curcumin to casein micelles. A fluorescence spectroscopy study. Food Chem. 2012, 132, 1143–1149.
  97. Elzoghby, A.O.; Helmy, M.W.; Samy, W.M.; Elgindy, N.A. Micellar Delivery of Flutamide Via Milk Protein Nanovehicles Enhances its Anti-Tumor Efficacy in Androgen-Dependent Prostate Cancer Rat Model. Pharm. Res. 2013, 30, 2654–2663.
  98. Elzoghby, A.O.; Helmy, M.W.; Samy, W.M.; Elgindy, N.A. Spray-dried casein-based micelles as a vehicle for solubilization and controlled delivery of flutamide: Formulation, characterization, and in vivo pharmacokinetics. Eur. J. Pharm. Biopharm. 2013, 84, 487–496.
  99. Khanji, A.N.; Michaux, F.; Petit, J.; Salameh, D.; Rizk, T.; Jasniewski, J.; Banon, S. Structure, gelation, and antioxidant properties of curcumin-doped casein micelle powder produced by spray-drying. Food Funct. 2018, 9, 971–981.
  100. Khanji, A.N.; Michaux, F.; Salameh, D.; Rizk, T.; Banon, S.; Jasniewski, J. The study of curcumin interaction with micellar casein and lactic acid bacteria cell envelope. LWT 2018, 91, 293–302.
  101. Chen, F.; Liang, L.; Zhang, Z.; Deng, Z.; Decker, E.A.; McClements, D.J. Inhibition of lipid oxidation in nanoemulsions and filled microgels fortified with omega-3 fatty acids using casein as a natural antioxidant. Food Hydrocoll. 2017, 63, 240–248.
  102. Loewen, A.; Chan, B.; Li-Chan, E.C. Optimization of vitamins A and D3 loading in re-assembled casein micelles and effect of loading on stability of vitamin D3 during storage. Food Chem. 2018, 240, 472–481.
  103. Bahri, A.; Henriquet, C.; Pugnière, M.; Marchesseau, S.; Chevalier-Lucia, D. Binding analysis between monomeric β-casein and hydrophobic bioactive compounds investigated by surface plasmon resonance and fluorescence spectroscopy. Food Chem. 2019, 286, 289–296.
  104. Ghasemi, S.; Abbasi, S. Formation of natural casein micelle nanocapsule by means of pH changes and ultrasound. Food Hydrocoll. 2014, 42, 42–47.
  105. Burgain, J.; Scher, J.; Lebeer, S.; Vanderleyden, J.; Cailliez-Grimal, C.; Corgneau, M.; Francius, G.; Gaiani, C. Significance of bacterial surface molecules interactions with milk proteins to enhance microencapsulation of Lactobacillus rhamnosus GG. Food Hydrocoll. 2014, 41, 60–70.
  106. Perlstein, H.; Bavli, Y.; Turovsky, T.; Rubinstein, A.; Danino, D.; Stepensky, D.; Barenholz, Y. Beta-casein nanocarriers of celecoxib for improved oral bioavailability. Eur. J. Nanomed. 2014, 6, 217–226.
  107. Yin, W.; Su, R.; Qi, W.; He, Z. A casein-polysaccharide hybrid hydrogel cross-linked by transglutaminase for drug delivery. J. Mater. Sci. 2012, 47, 2045–2055.
  108. Mohan, M.S.; Jurat-Fuentes, J.L.; Harte, F. Binding of vitamin A by casein micelles in commercial skim milk. J. Dairy Sci. 2013, 96, 790–798.
  109. Arranz, E.; Santoyo, S.; Jaime, L.; Fornari, T.; Reglero, G.; Guri, A.; Corredig, M. Improved Bioavailability of Supercritical Rosemary Extract Through Encapsulation in Different Delivery Systems after In Vitro Digestion. Food Dig. Res. Curr. Opin. 2015, 6, 30–37.
  110. Anema, S.G.; de Kruif, C.G. Lactoferrin binding to transglutaminase cross-linked casein micelles. Int. Dairy J. 2012, 26, 83–87.
  111. Elzoghby, A.O.; Samy, W.M.; Elgindy, N.A. Novel Spray-Dried Genipin-Crosslinked Casein Nanoparticles for Prolonged Release of Alfuzosin Hydrochloride. Pharm. Res. 2013, 30, 512–522.
  112. Mirpoor, S.F.; Hosseini, S.M.H.; Yousefi, G.H. Mixed biopolymer nanocomplexes conferred physicochemical stability and sustained release behavior to introduced curcumin. Food Hydrocoll. 2017, 71, 216–224.
  113. Hasni, I.; Bourassa, P.; Hamdani, S.; Samson, G.; Carpentier, R.; Tajmir-Riahi, H.-A. Interaction of milk α- and β-caseins with tea polyphenols. Food Chem. 2011, 126, 630–639.
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