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Enteric-coated capsule containing β-galactosidase-loaded polylactic acid nanocapsules: enzyme stability and milk lactose hydrolysis under simulated gastrointestinal conditions

Published online by Cambridge University Press:  29 September 2014

Hongjun He*
Affiliation:
College of Life Sciences, Yantai University, Yantai 264005, PR China
Xueting Zhang
Affiliation:
College of Life Sciences, Yantai University, Yantai 264005, PR China
Yan Sheng
Affiliation:
College of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, PR China
*
*For correspondence; e-mail: hemiles@163.com

Abstract

In order to protect peroral β-galactosidase from being degraded and hydrolyse milk lactose efficiently in the environments of gastrointestinal tract, a double-capsule delivery system composed of enteric-coated capsule and polylactic acid (PLA) nanocapsules (NCs) was developed for encapsulation of β-galactosidase. β-galactosidase-loaded PLA NCs in the size range of 100–200 nm were prepared by a modified w1/o/w2 technique. During the encapsulation process, dichloromethane/ethyl acetate (1 : 1, v/v) as the solvent composition, high-pressure homogenisation (150 bar, 3 min) as the second emulsification method and polyvinyl alcohol or Poloxamer 188 as a stabiliser in the inner phase could efficiently improve the activity retention of β-galactosidase (>90%). Subsequently, the prepared NCs were freeze-dried and filled in a hydroxypropyl methylcellulose phthalate (HP55)-coated capsule. In vitro results revealed that the HP55-coated capsule remained intact in the simulated gastric fluid and efficiently protected the nested β-galactosidase from acidic denaturation. Under the simulated intestinal condition, the enteric coating dissolved rapidly and released the β-galactosidase-loaded PLA NCs, which exhibited greater stability against enzymatic degradation and higher hydrolysis ratio (∼100%) towards milk lactose than the free β-galactosidase. These results suggest that this double-capsule delivery system represents promising candidate for efficient lactose hydrolysis in the gastrointestinal tract.

Type
Research Article
Copyright
Copyright © Proprietors of Journal of Dairy Research 2014 

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References

Abdelwahed, W, Degobert, G, Stainmesse, S & Fessi, H 2006a Freeze-drying of nanoparticles: formulation, process and storage considerations. Advanced Drug Delivery Reviews 58 16881713 Google Scholar
Abdelwahed, W, Degobert, G & Fessi, H 2006b A pilot study of freeze drying of poly(epsilon-caprolactone) nanocapsules stabilized by poly(vinyl alcohol): formulation and process optimization. International Journal of Pharmaceutics 309 178188 Google Scholar
Casellas, F, Varela, E, Aparici, A, Casaus, M & Rodriguez, P 2009 Development, validation, and applicability of a symptoms questionnaire for lactose malabsorption screening. Digestive Diseases and Sciences 54 10591065 Google Scholar
Cui, FD, Tao, AJ, Cun, DM, Zhang, LQ & Shi, K 2007 Preparation of insulin loaded PLGA-Hp55 nanoparticles for oral delivery. Journal of Pharmaceutical Sciences 96 421427 Google Scholar
Dziubla, TD, Shuvaev, VV, Hong, NK, Hawkins, BJ, Madesh, M, Takano, H, Simone, E, Nakada, MT, Fisher, A, Albelda, SM & Muzykantov, VR 2008 Endothelial targeting of semi-permeable polymer nanocarriers for enzyme therapies. Biomaterials 29 215227 Google Scholar
Gamboa, JM & Leong, KW 2013 In vitro and in vivo models for the study of oral delivery of nanoparticles. Advanced Drug Delivery Reviews 65 800810 CrossRefGoogle Scholar
Gander, B, Wehrli, E, Alder, R & Merkle, HP 1995 Quality improvement of spay-dried, protein-loaded D,L-PLA microspheres by appropriate polymer-solvent selection. Journal of Microencapsulation 12 8397 Google Scholar
Gilat, T, Russo, S, Gelman-Malachi, E & Aldor, TA 1972 Lactase in man: a nonadaptable enzyme. Gastroenterology 62 11251127 Google Scholar
Harrington, LK & Mayberry, JF 2008 A re-appraisal of lactose intolerance. International Journal of Clinical Practice 62 15411546 Google Scholar
Kwak, HS, Kwon, SH, Lee, JB & Ahn, J 2002 In vitro stability of β-galactosidase microcapsules. Asian-Australasian Journal of Animal Sciences 15 18081812 Google Scholar
Lain, C 2009 The mouth, stomach and intestines. Anaesthesia and Intensive Care 10 336338 Google Scholar
Li, XH, Zhang, YH, Yan, RH, Jia, WX, Yuan, ML, Deng, XM & Huang, ZT 2000 Influence of process parameters on the protein stability encapsulated in poly-DL-lactide–poly(ethylene glycol) microspheres. Journal of Controlled Release 68 4152 CrossRefGoogle ScholarPubMed
Lin, M-Y, Dipalma, JA, Martini, MC, Gross, CJ, Harlander, SK & Savaiano, DA 1993 Comparative effects of exogenous lactase (β-galactosidase) preparations on in vivo lactose digestion. Digestive Diseases and Sciences 38 20222027 Google Scholar
Montalto, M, Nucera, G, Santoro, L, Curigliano, V, Vastola, M, Covino, M, Cuoco, L, Manna, R, Gasbarrini, A & Gasbarrini, G 2005 Effect of exogenous β-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study. European Journal of Clinical Nutrition 59 489493 Google Scholar
Montalto, M, Curigliano, V, Santoro, L, Vastola, M, Cammarota, G & Manna, R 2006 Management and treatment of lactose malabsorption. World Journal of Gastroenterology 12 187191 Google Scholar
Ramirez, FC, Lee, K & Graham, DY 1994 All lactase preparations are not the same: results of a prospective, randomized, placebo-controlled trial. American Journal of Gastroenterology 89 566570 Google Scholar
Sajeesh, S, Vauthier, C, Gueutin, C, Ponchel, G & Sharma, CP 2010 Thiol functionalized polymethacrylic acid-based hydrogel microparticles. Acta Biomaterials 6 30723080 Google Scholar
Schmolka, IR 1991 A comparison of block copolymer surfactant gels. Journal of American Oil Chemists’ Society 68 206209 Google Scholar
Schultz, S, Wagner, G, Urban, K & Ulrich, J 2004 High-pressure homogenization as a process for emulsion formation. Chemical Engineering & Technology 27 361368 Google Scholar
Sheng, Y, Liu, CS, Yuan, Y, Zhang, XL, Shan, XQ & Xu, F 2009a Porosity and semipermeability of hemoglobin-loaded polymeric nanoparticles as potential blood substitutes. Journal of Biomedical Materials Research Part B:Applied Biomaterials 91B 631642 Google Scholar
Sheng, Y, Yuan, Y, Liu, CS, Tao, XY, Shan, XQ & Xu, F 2009b In vitro macrophage uptake and in vivo biodistribution of PLA–PEG nanoparticles loaded with hemoglobin as blood substitutes: effect of PEG content. Journal of Materials Science: Materials in Medicine 20 18811891 Google Scholar
Shi, AM, Wang, LJ, Li, D & Adhikari, B 2012 The effect of annealing and cryoprotectants on the properties of vacuum-freeze dried starch nanoparticles. Carbohydrate Polymers 88 13341341 Google Scholar
Sturesson, C & Carlfors, J 2000 Incorporation of protein in PLG-microspheres with retention of bioactivity. Journal of Controlled Release 67 171178 Google Scholar
Wang, H, Luo, HY, Bai, YG, Wang, Y, Yang, PL, Shi, PJ, Zhang, W, Fan, YL & Yao, B 2009 An acidophilic β-galactosidase from bispora sp. MEY-1 with high lactose hydrolytic activity under simulated gastric conditions. Journal of Agricultural and Food Chemistry 57 55355541 Google Scholar
Weert, M, Hoechstetter, J, Hennink, WE & Crommelin, DJA 2000 The effect of a water/organic solvent interface on the structural stability of lysozyme. Journal of Controlled Release 68 351359 CrossRefGoogle ScholarPubMed