Full Text:   <1972>

Summary:  <1496>

CLC number: TS253.1

On-line Access: 2020-08-04

Received: 2020-04-02

Revision Accepted: 2020-06-02

Crosschecked: 2020-07-20

Cited: 0

Clicked: 2926

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.8 P.611-627


Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion

Author(s):  Jin Zhang, Huan-Huan Li, Yi-Fan Chen, Li-Hong Chen, Hong-Gang Tang, Fan-Bin Kong, Yun-Xin Yao, Xu-Ming Liu, Qian Lan, Xiao-Fan Yu

Affiliation(s):  Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; more

Corresponding email(s):   cwc528@163.com, zaastang@163.com

Key Words:  Immunoglobulin Y (IgY), Microencapsulation, Chitooligosaccharide (COS), Response surface methodology (RSM), Controlled release, Simulated gastrointestinal digestion (SGID)

Jin Zhang, Huan-Huan Li, Yi-Fan Chen, Li-Hong Chen, Hong-Gang Tang, Fan-Bin Kong, Yun-Xin Yao, Xu-Ming Liu, Qian Lan, Xiao-Fan Yu. Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion[J]. Journal of Zhejiang University Science B, 2020, 21(8): 611-627.

@article{title="Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion",
author="Jin Zhang, Huan-Huan Li, Yi-Fan Chen, Li-Hong Chen, Hong-Gang Tang, Fan-Bin Kong, Yun-Xin Yao, Xu-Ming Liu, Qian Lan, Xiao-Fan Yu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion
%A Jin Zhang
%A Huan-Huan Li
%A Yi-Fan Chen
%A Li-Hong Chen
%A Hong-Gang Tang
%A Fan-Bin Kong
%A Yun-Xin Yao
%A Xu-Ming Liu
%A Qian Lan
%A Xiao-Fan Yu
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 8
%P 611-627
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000172

T1 - Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion
A1 - Jin Zhang
A1 - Huan-Huan Li
A1 - Yi-Fan Chen
A1 - Li-Hong Chen
A1 - Hong-Gang Tang
A1 - Fan-Bin Kong
A1 - Yun-Xin Yao
A1 - Xu-Ming Liu
A1 - Qian Lan
A1 - Xiao-Fan Yu
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 8
SP - 611
EP - 627
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000172

immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.


结论:采用响应面法优化的微胶囊配方工艺为海藻酸钠浓度1.56%(15.6 g/L)、壳寡糖浓度0.61%(6.1 g/L)和IgY/海藻酸钠比率62.44%(质量比),由此制备的微胶囊包埋率达65.19%,负载率达33.75%,平均粒径为588.75 μm.壳寡糖涂层通过填充效应和静电相互作用使微胶囊表面更加光滑和连续,从而显著降低了模拟胃肠道消化过程中IgY的释放速率.微胶囊中IgY的模拟胃部控释和模拟肠道控释分别符合零级动力学方程和一级动力学方程(R2>0.99).微胶囊在模拟胃肠道消化4 h后的IgY免疫活性保持率达84.37%,远高于未进行微胶囊化保护的IgY(5.33%).


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Anal AK, Bhopatkar D, Tokura S, et al., 2003. Chitosan-alginate multilayer beads for gastric passage and controlled intestinal release of protein. Drug Dev Ind Pharm, 29(6):713-724.

[2]Bakhshi M, Ebrahimi F, Nazarian S, et al., 2017. Nano-encapsulation of chicken immunoglobulin (IgY) in sodium alginate nanoparticles: in vitro characterization. Biologicals, 49:69-75.

[3]Cai YC, Guo J, Chen SH, et al., 2012. Chicken egg yolk antibodies (IgY) for detecting circulating antigens of Schistosoma japonicum. Parasitol Int, 61(3):385-390.

[4]Carlander D, Kollberg H, Wejåker PE, et al., 2000. Peroral immunotheraphy with yolk antibodies for the prevention and treatment of enteric infections. Immunol Res, 21(1):1-6.

[5]Chandika P, Ko SC, Oh GW, et al., 2015. Fish collagen/ alginate/chitooligosaccharides integrated scaffold for skin tissue regeneration application. Int J Biol Macromol, 81: 504-513.

[6]Dávalos-Pantoja L, Ortega-Vinuesa JL, Bastos-González D, et al., 2000. A comparative study between the adsorption of IgY and IgG on latex particles. J Biomater Sci Polym Ed, 11(6):657-673.

[7]Eltayeb M, Stride E, Edirisinghe M, 2015. Preparation, characterization and release kinetics of ethylcellulose nanoparticles encapsulating ethylvanillin as a model functional component. J Funct Foods, 14:726-735.

[8]Gandomi H, Abbaszadeh S, Misaghi A, et al., 2016. Effect of chitosan-alginate encapsulation with inulin on survival of Lactobacillus rhamnosus GG during apple juice storage and under simulated gastrointestinal conditions. LWT-Food Sci Technol, 69:365-371.

[9]Gåserød O, Smidsrød O, Skjåk-Bræk G, 1998. Microcapsules of alginate-chitosan–I: a quantitative study of the interaction between alginate and chitosan. Biomaterials, 19(20):1815-1825.

[10]Ha HK, Kim JW, Lee MR, et al., 2013. Formation and characterization of quercetin-loaded chitosan oligosaccharide/ β-lactoglobulin nanoparticle. Food Res Int, 52(1):82-90.

[11]He SD, Zhang Y, Sun HJ, et al., 2019. Antioxidative peptides from proteolytic hydrolysates of false abalone (Volutharpa ampullacea perryi):characterization, identification, and molecular docking. Mar Drugs, 17(2):116.

[12]Higuchi T, 1963. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci, 52(12):1145-1149.

[13]Igathinathane C, Ulusoy U, 2016. Machine vision methods based particle size distribution of ball- and gyro-milled lignite and hard coal. Powder Technol, 297:71-80.

[14]Jain S, Anal AK, 2016. Optimization of extraction of functional protein hydrolysates from chicken egg shell membrane (ESM) by ultrasonic assisted extraction (UAE) and enzymatic hydrolysis. LWT-Food Sci Technol, 69:295-302.

[15]Jeong C, Kim S, Lee C, et al., 2020. Changes in the physical properties of calcium alginate gel beads under a wide range of gelation temperature conditions. Foods, 9(2):180.

[16]Kovacs-Nolan J, Mine Y, 2012. Egg yolk antibodies for passive immunity. Annu Rev Food Sci Technol, 3:163-182.

[17]Kumar Giri T, Thakur D, Alexander A, et al., 2012. Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications. Curr Drug Deliv, 9(6):539-555.

[18]Lee J, Kang HE, Woo HJ, 2012. Stability of orally administered immunoglobulin in the gastrointestinal tract. J Immunol Methods, 384(1-2):143-147.

[19]Li XY, Wu MB, Xiao M, et al., 2019. Microencapsulated β-carotene preparation using different drying treatments. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(11):901-909.

[20]Lian ZR, Pan R, Wang JT, 2016. Microencapsulation of norfloxacin in chitosan/chitosan oligosaccharides and its application in shrimp culture. Int J Biol Macromol, 92:587-592.

[21]Liu CZ, Liu ZZ, Sun X, et al., 2018. Fabrication and characterization of β-lactoglobulin-based nanocomplexes composed of chitosan oligosaccharides as vehicles for delivery of astaxanthin. J Agric Food Chem, 66(26):6717-6726.

[22]Lu CH, Engelmann NJ, Lila MA, et al., 2008. Optimization of lycopene extraction from tomato cell suspension culture by response surface methodology. J Agric Food Chem, 56(17):7710-7714.

[23]Mahasukhonthachat K, Sopade PA, Gidley MJ, 2010. Kinetics of starch digestion in sorghum as affected by particle size. J Food Eng, 96(1):18-28.

[24]Marcet I, Salvadores M, Rendueles M, et al., 2018. The effect of ultrasound on the alkali extraction of proteins from eggshell membranes. J Sci Food Agric, 98(5):1765-1772.

[25]Mohammadi R, Mohammadifar MA, Mortazavian AM, et al., 2016. Extraction optimization of pepsin-soluble collagen from eggshell membrane by response surface methodology (RSM). Food Chem, 190:186-193.

[26]Otsuka M, Matsuda Y, 1996. Comparative evaluation of mean particle size of bulk drug powder in pharmaceutical preparations by fourier-transformed powder diffuse reflectance infrared spectroscopy and dissolution kinetics. J Pharm Sci, 85(1):112-116.

[27]Pauly D, Chacana PA, Calzado EG, et al., 2011. IgY technology: extraction of chicken antibodies from egg yolk by polyethylene glycol (PEG) precipitation. J Vis Exp, (51):e3084.

[28]Pereira EPV, van Tilburg MF, Florean EOPT, et al., 2019. Egg yolk antibodies (IgY) and their applications in human and veterinary health: a review. Int Immunopharmacol, 73: 293-303.

[29]Rahman S, van Nguyen S, Icatlo FC Jr, et al., 2013. Oral passive IgY-based immunotherapeutics: a novel solution for prevention and treatment of alimentary tract diseases. Hum Vacc Immunother, 9(5):1039-1048.

[30]Ren ZY, Zhang XR, Guo Y, et al., 2017. Preparation and in vitro delivery performance of chitosan–alginate microcapsule for IgG. Food Agric Immunol, 28(1):1-13.

[31]Ritger PL, Peppas NA, 1987. A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Controlled Release, 5(1):23-36.

[32]Rosa-Sibakov N, Sibakov J, Lahtinen P, et al., 2015. Wet grinding and microfluidization of wheat bran preparations: improvement of dispersion stability by structural disintegration. J Cereal Sci, 64:1-10.

[33]Scheraiber M, Grześkowiak Ł, Zentek J, et al., 2019. Inclusion of IgY in a dog’s diet has moderate impact on the intestinal microbial fermentation. J Appl Microbiol, 127(4):996-1003.

[34]Vueba ML, Batista de Carvalho LAE, Veiga F, et al., 2004. Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets. Eur J Pharm Biopharm, 58(1):51-59.

[35]Wang T, He N, 2010. Preparation, characterization and applications of low-molecular-weight alginate-oligochitosan nanocapsules. Nanoscale, 2(2):230-239.

[36]Wang YL, Khan A, Liu YX, et al., 2019. Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs. Carbohydr Polym, 223: 115061.

[37]Wei TT, Hishikawa A, Shimizu Y, et al., 2014. Particulate characterization of bovine bone granules pulverized with a high-speed blade mill. Powder Technol, 261:147-153.

[38]Xing PP, Shi YN, Dong CC, et al., 2017. Colon-targeted delivery of IgY against Clostridium difficile toxin A and B by encapsulation in chitosan-Ca pectinate microbeads. AAPS PharmSciTech, 18(4):1095-1103.

[39]Xu YF, Lin H, Sui JX, et al., 2012. Effects of specific egg yolk antibody (IgY) on the quality and shelf life of refrigerated Paralichthys olivaceus. J Sci Food Agric, 92(6):1267-1272.

[40]Zhang J, Yin T, Xiong SB, et al., 2016. Thermal treatments affect breakage kinetics and calcium release of fish bone particles during high-energy wet ball milling. J Food Eng, 183:74-80.

[41]Zhang J, He SX, Kong FB, et al., 2017. Size reduction and calcium release of fish bone particles during nanomilling as affected by bone structure. Food Bioprocess Technol, 10(12):2176-2187.

[42]Zhang J, Du HY, Zhang GN, et al., 2020. Identification and characterization of novel antioxidant peptides from crucian carp (Carassius auratus) cooking juice released in simulated gastrointestinal digestion by UPLC-MS/MS and in silico analysis. J Chromatogr B, 1136:121893.

[43]Zhang YL, Wei W, Lv PP, et al., 2011. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur J Pharm Biopharm, 77(1):11-19.

[44]Zimet P, Mombrú ÁW, Faccio R, et al., 2018. Optimization and characterization of nisin-loaded alginate-chitosan nanoparticles with antimicrobial activity in lean beef. LWT, 91:107-116.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE