{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:56:37Z","timestamp":1791251797699,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Assignment of the Russian Federation","award":["075-00224-24-03"],"award-info":[{"award-number":["075-00224-24-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>More than half of the global population is unable to consume dairy products due to lactose intolerance (hypolactasia). Current enzyme replacement therapy methods are insufficiently effective as a therapeutic approach to treating lactose intolerance. The encapsulation of \u03b2-galactosidase in polyelectrolyte microcapsules by using the layer-by-layer method could be a possible solution to this problem. In this study, adsorption and co-precipitation methods were employed for encapsulating \u03b2-galactosidase in polyelectrolyte microcapsules composed of (polyallylamine \/polystyrene sulphonate)\u2083. As a result, the co-precipitation method was chosen for \u03b2-galactosidase encapsulation. The adsorption method permits to encapsulate six times less enzyme compared with the co-precipitation method; the \u03b2-galactosidase encapsulated via the co-precipitation method released no more than 20% of the initially encapsulated enzyme in pH 2 or 1 M NaCl solutions. In contrast, when using the sorption method, about 100% of the initially encapsulated enzyme was released from the microcapsules under the conditions described above. The co-precipitation method effectively prevents the complete loss of enzyme activity after 2 h of incubation in a solution with pH 2 while also alleviating the adverse effects of ionic strength. Consequently, the encapsulated form of \u03b2-galactosidase shows promise as a potential therapeutic agent for enzyme replacement therapy in the treatment of hypolactasia.<\/jats:p>","DOI":"10.3390\/ijms252010978","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:02:58Z","timestamp":1728878578000},"page":"10978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Encapsulation of \u03b2-Galactosidase into Polyallylamine\/Polystyrene Sulphonate Polyelectrolyte Microcapsules"],"prefix":"10.3390","volume":"25","author":[{"given":"Yuri S.","family":"Chebykin","sequence":"first","affiliation":[{"name":"Institute of Theoretical and Experimental Biophysics Russian Academy of Science, Institutskaya St., 3, 142290 Puschino, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-2042","authenticated-orcid":false,"given":"Egor V.","family":"Musin","sequence":"additional","affiliation":[{"name":"Institute of Theoretical and Experimental Biophysics Russian Academy of Science, Institutskaya St., 3, 142290 Puschino, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-9635","authenticated-orcid":false,"given":"Aleksandr L.","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Theoretical and Experimental Biophysics Russian Academy of Science, Institutskaya St., 3, 142290 Puschino, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0537-9537","authenticated-orcid":false,"given":"Sergey A.","family":"Tikhonenko","sequence":"additional","affiliation":[{"name":"Institute of Theoretical and Experimental Biophysics Russian Academy of Science, Institutskaya St., 3, 142290 Puschino, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Haug, A., H\u00f8stmark, A.T., and Harstad, O.M. (2007). Bovine milk in human nutrition\u2014A review. Lipids Health Dis., 6\u201325.","DOI":"10.1186\/1476-511X-6-25"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3945\/an.113.005025","article-title":"Milk, Dairy Products, and Their Functional Effects in Humans: A Narrative Review of Recent Evidence","volume":"5","author":"Visioli","year":"2014","journal-title":"Adv. Nutr. Int. Rev. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1256S","DOI":"10.3945\/ajcn.113.073056","article-title":"Dairy products, yogurts, and bone health","volume":"99","author":"Rizzoli","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1093\/ajcn\/76.3.675","article-title":"Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health","volume":"76","author":"Williams","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3945\/jn.109.118539","article-title":"Estimation of Total Usual Calcium and Vitamin D Intakes in the United States","volume":"140","author":"Bailey","year":"2010","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1080\/10408398.2017.1392288","article-title":"Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies","volume":"59","author":"Bechthold","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.3168\/jds.2017-13419","article-title":"Technical note: Development and validation of a new method for the quantification of soluble and micellar calcium, magnesium, and potassium in milk","volume":"101","author":"Franzoi","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S2468-1253(17)30154-1","article-title":"Country, regional, and global estimates for lactose malabsorption in adults: A systematic review and meta-analysis","volume":"2","author":"Storhaug","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Szilagyi, A., and Ishayek, N. (2018). Lactose Intolerance, Dairy Avoidance, and Treatment Options. Nutrients, 10.","DOI":"10.3390\/nu10121994"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"De Gregorio, P.R., Gennari, A., Nied, C.V., Volpato, G., and Volken de Souza, C.F. (2023). Low-lactose milk production using \u03b2-galactosidases. Enzymes beyond Traditional Applications in Dairy Science and Technology, Elsevier.","DOI":"10.1016\/B978-0-323-96010-6.00014-X"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dominici, S., Marescotti, F., Sanmartin, C., Macaluso, M., Taglieri, I., Venturi, F., Zinnai, A., and Facioni, M.S. (2022). Lactose: Characteristics, Food and Drug-Related Applications, and Its Possible Substitutions in Meeting the Needs of People with Lactose Intolerance. Foods, 11.","DOI":"10.3390\/foods11101486"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hebbink, G.A., and Dickhoff, B.H.J. (2019). Application of lactose in the pharmaceutical industry. Lactose, Elsevier.","DOI":"10.1016\/B978-0-12-811720-0.00005-2"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, A., Zheng, J., Han, X., Jiang, Z., Yang, B., Yang, S., Zhou, W., Li, C., and Sun, M. (2023). Health implication of lactose intolerance and updates on its dietary management. Int. Dairy J., 140.","DOI":"10.1016\/j.idairyj.2023.105608"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1155\/2015\/904686","article-title":"Adult Lactose Digestion Status and Effects on Disease","volume":"29","author":"Szilagyi","year":"2015","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"198S","DOI":"10.1080\/07315724.2001.10719032","article-title":"Lactose Maldigestion, Calcium Intake and Osteoporosis in African-, Asian-, and Hispanic-Americans","volume":"20","author":"Jackson","year":"2001","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_16","first-page":"G802","article-title":"Luminal hypertonicity and acidity modulate colorectal afferents and induce persistent visceral hypersensitivity","volume":"303","author":"La","year":"2012","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/0884533612440289","article-title":"Beneficial Effects of Long-Term Consumption of a Probiotic Combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult May Persist After Suspension of Therapy in Lactose-Intolerant Patients","volume":"27","author":"Almeida","year":"2012","journal-title":"Nutr. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12937-016-0172-y","article-title":"The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance\u2014A randomized, double-blind, placebo-controlled, crossover clinical trial","volume":"15","author":"Pakdaman","year":"2015","journal-title":"Nutr. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Arnold, J.W., Simpson, J.B., Roach, J., Bruno-Barcena, J.M., and Azcarate-Peril, M.A. (2018). Prebiotics for Lactose Intolerance: Variability in Galacto-Oligosaccharide Utilization by Intestinal Lactobacillus rhamnosus. Nutrients, 10.","DOI":"10.3390\/nu10101517"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijbiomac.2013.05.003","article-title":"The crystal structure of acidic \u03b2-galactosidase from Aspergillus oryzae","volume":"60","author":"Maksimainen","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129050","DOI":"10.1016\/j.foodchem.2021.129050","article-title":"\u03b2-galactosidase from Kluyveromyces lactis in genipin-activated chitosan: An investigation on immobilization, stability, and application in diluted UHT milk","volume":"349","author":"Lima","year":"2021","journal-title":"Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s11095-013-1233-y","article-title":"Improving the Stability and Activity of Oral Therapeutic Enzymes\u2014Recent Advances and Perspectives","volume":"31","author":"Fuhrmann","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fraile-Guti\u00e9rrez, I., Iglesias, S., Acosta, N., and Revuelta, J. (2024). Chitosan-based oral hydrogel formulations of \u03b2-galactosidase to improve enzyme supplementation therapy for lactose intolerance. Int. J. Biol. Macromol., 255.","DOI":"10.1016\/j.ijbiomac.2023.127755"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.foodchem.2015.01.088","article-title":"Immobilization and controlled release of \u03b2-galactosidase from chitosan-grafted hydrogels","volume":"179","author":"Facin","year":"2015","journal-title":"Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.procbio.2022.08.026","article-title":"Anchoring lactase in pectin-based hydrogels for lactose hydrolysis reactions","volume":"122","author":"Hanauer","year":"2022","journal-title":"Process. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cargnin, M.A., Gasparin, B.C., Rosa, D.d.S., and Paulino, A.T. (2021). Performance of lactase encapsulated in pectin-based hydrogels during lactose hydrolysis reactions. LWT, 150.","DOI":"10.1016\/j.lwt.2021.111863"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bai, Y., and Gilbert, R.G. (2022). Mechanistic Understanding of the Effects of Pectin on In Vivo Starch Digestion: A Review. Nutrients, 14.","DOI":"10.3390\/nu14235107"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cao, W., Guan, S., Yuan, Y., Wang, Y., Nushrat, Y.M., Liu, Y., Tong, Y., Yu, S., and Hua, X. (2023). The digestive behavior of pectin in human gastrointestinal tract: a review on fermentation characteristics and degradation mechanism. Crit. Rev. Food Sci. Nutr., 1\u201324.","DOI":"10.1080\/10408398.2023.2253547"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118830","DOI":"10.1016\/j.carbpol.2021.118830","article-title":"Dietary \u03ba-carrageenan facilitates gut microbiota-mediated intestinal inflammation","volume":"277","author":"Wu","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1021\/bp0495825","article-title":"Protein-Calcium Carbonate Coprecipitation: A Tool for Protein Encapsulation","volume":"21","author":"Petrov","year":"2005","journal-title":"Biotechnol. Prog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/bit.1184","article-title":"Encapsulation of proteins by layer-by-layer adsorption of polyelectrolytes onto protein aggregates: Factors regulating the protein release","volume":"76","author":"Balabushevitch","year":"2001","journal-title":"Biotechnol. Bioeng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13159","DOI":"10.1021\/jp0511092","article-title":"Charge-Controlled Permeability of Polyelectrolyte Microcapsules","volume":"109","author":"Tong","year":"2005","journal-title":"J. Phys. Chem. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.2116\/analsci.19P131","article-title":"Comparative Study of Electrochemical Sensors Based on Enzyme Immobilized into Polyelectrolyte Microcapsules and into Chitosan Gel","volume":"35","author":"Plekhanova","year":"2019","journal-title":"Anal. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Reshetilov, A., Plekhanova, Y., Tarasov, S., Tikhonenko, S., Dubrovsky, A., Kim, A., Kashin, V., Machulin, A., Wang, G.-J., and Kolesov, V. (2019). Bioelectrochemical Properties of Enzyme-Containing Multilayer Polyelectrolyte Microcapsules Modified with Multiwalled Carbon Nanotubes. Membranes, 9.","DOI":"10.3390\/membranes9040053"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1007\/s00216-012-6381-0","article-title":"Chemosensors and biosensors based on polyelectrolyte microcapsules containing fluorescent dyes and enzymes","volume":"405","author":"Kazakova","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1134\/S0006350907060085","article-title":"Protein-filled polyelectrolyte microcapsules in the design of enzymic microdiagnostics","volume":"52","author":"Sukhorukov","year":"2007","journal-title":"Biophysics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1021\/nl0100015","article-title":"Urease Encapsulation in Nanoorganized Microshells","volume":"1","author":"Lvov","year":"2001","journal-title":"Nano Lett."},{"key":"ref_38","first-page":"1041","article-title":"Incapsulation of enzymes into polyelectrolyte nano- and microcapsules and the problem of the development of enzymatic microdiagnostics","volume":"52","author":"Dybovskaia","year":"2008","journal-title":"Biofizika"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, A.L., Musin, E.V., Dubrovskii, A.V., and Tikhonenko, S.A. (2020). Effect of Pollyallylamine on Alcoholdehydrogenase Structure and Activity. Polymers, 12.","DOI":"10.3390\/polym12040832"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9002","DOI":"10.1021\/acsomega.7b01230","article-title":"Intracellular Delivery of \u03b2-Galactosidase Enzyme Using Arginase-Responsive Dextran Sulfate\/Polyarginine Capsule for Lysosomal Storage Disorder","volume":"2","author":"Gupta","year":"2017","journal-title":"ACS Omega"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, A.L., Musin, E.V., Chebykin, Y.S., and Tikhonenko, S.A. (2024). Characterization of Polyallylamine\/Polystyrene Sulfonate Polyelectrolyte Microcapsules Formed on Solid Cores: Morphology. Polymers, 16.","DOI":"10.3390\/polym16111521"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14040","DOI":"10.1038\/s41598-021-93565-2","article-title":"New sight at the organization of layers of multilayer polyelectrolyte microcapsules","volume":"11","author":"Musin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1021\/la036177z","article-title":"Matrix Polyelectrolyte Microcapsules: New System for Macromolecule Encapsulation","volume":"20","author":"Volodkin","year":"2004","journal-title":"Langmuir"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113915","DOI":"10.1016\/j.addr.2021.113915","article-title":"In vivo models to evaluate ingestible devices: Present status and current trends","volume":"177","author":"Stamatopoulos","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.3748\/wjg.v26.i43.6706","article-title":"Gastric acid level of humans must decrease in the future","volume":"26","author":"Fujimori","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.3748\/wjg.v16.i43.5496","article-title":"Gastric juice acidity in upper gastrointestinal diseases","volume":"16","author":"Lu","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"118530","DOI":"10.1016\/j.carbpol.2021.118530","article-title":"Colon-targeted drug delivery of polysaccharide-based nanocarriers for synergistic treatment of inflammatory bowel disease: A review","volume":"272","author":"Cui","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_48","first-page":"5","article-title":"Duodenal mucosal protection by bicarbonate secretion and its mechanisms","volume":"2","author":"Konturek","year":"2004","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yuan, Q., Pan, A., Fu, Y., and Dai, Y. (2021). Anatomy and physiology of the pancreas. Integrative Pancreatic Intervention Therapy, Elsevier.","DOI":"10.1016\/B978-0-12-819402-7.00001-2"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cis.2004.07.006","article-title":"Polyelectrolyte multilayer capsules as vehicles with tunable permeability","volume":"111","author":"Antipov","year":"2004","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8659","DOI":"10.1039\/c2sm25971k","article-title":"pH- and salt-mediated response of layer-by-layer assembled PSS\/PAH microcapsules: Fusion and polymer exchange","volume":"8","author":"Pechenkin","year":"2012","journal-title":"Soft Matter"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dubrovskii, A.V., Kim, A.L., Musin, E.V., Ramazanov, B.R., and Tikhonenko, S.A. (2021). The Discovery of the Buffer Capacity of Various Types of Polyelectrolyte Microcapsules. Polymers, 13.","DOI":"10.3390\/polym13224026"},{"key":"ref_53","unstructured":"(2024, August 31). The Composition of Intestinal Secretions. Available online: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0021925818753143?ref=pdf_download&fr=RR-2&rr=8d136494bf5ece44."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1136\/gut.33.12.1617","article-title":"Concentrations of metals in gastric juice in health and peptic ulcer disease","volume":"33","author":"Powell","year":"1992","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s12276-023-00960-y","article-title":"Intestinal mucus components and secretion mechanisms: What we do and do not know","volume":"55","author":"Song","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0927-7757(03)00195-X","article-title":"Carbonate microparticles for hollow polyelectrolyte capsules fabrication","volume":"224","author":"Shchukin","year":"2003","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ibrahim, N.A., Eid, B.M., and Amin, H.A. (2021). Sustainable textile finishing processes and pollution control based on enzyme technology. Green Chemistry for Sustainable Textiles, Elsevier.","DOI":"10.1016\/B978-0-323-85204-3.00018-X"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.pisc.2014.02.006","article-title":"Current IUBMB recommendations on enzyme nomenclature and kinetics","volume":"1","year":"2014","journal-title":"Perspect. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:57Z","timestamp":1760112717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,12]]},"references-count":58,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms252010978"],"URL":"https:\/\/doi.org\/10.3390\/ijms252010978","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,12]]}}}