Browse > Article
http://dx.doi.org/10.4014/jmb.1811.11021

Oral Delivery of Probiotics Using pH-Sensitive Phthalyl Inulin Tablets  

Kim, Whee-Soo (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
Cho, Chong-Su (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
Hong, Liang (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
Han, Geon Goo (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
Kil, Bum Ju (WCU Biomodulation Major and Center for Food and Bioconvergence, Seoul National University)
Kang, Sang-Kee (Institute of Green-Bio Science & Technology, Seoul National University)
Kim, Dae-Duk (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Choi, Yun-Jaie (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
Huh, Chul Sung (Institute of Green-Bio Science & Technology, Seoul National University)
Publication Information
Journal of Microbiology and Biotechnology / v.29, no.2, 2019 , pp. 200-208 More about this Journal
Abstract
Probiotics show low cell viability after oral administration because they have difficulty surviving in the stomach due to low pH and enzymes. For the oral delivery of probiotics, developing a formula that protects the probiotic bacteria from gastric acidity while providing living cells is mandatory. In this study, we developed tablets using a new pH-sensitive phthalyl inulin (PI) to protect probiotics from gastric conditions and investigated the effects of different compression forces on cell survival. We made three different tablets under different compression forces and measured survivability, disintegration time, and kinetics in simulated gastric-intestinal fluid. During tableting, there were no significant differences in probiotic viability among the different compression forces although disintegration time was affected by the compression force. A higher compression force resulted in higher viability in simulated gastric fluid. The swelling degree of the PI tablets in simulated intestinal fluid was higher than that of the tablets in simulated gastric fluid due to the pH sensitivity of the PI. The probiotic viability formulated in the tablets was also higher in acidic gastric conditions than that for probiotics in solution. Rapid release of the probiotics from the tablet occurred in the simulated intestinal fluid due to the pH sensitivity. After 6 months of refrigeration, the viability of the PI probiotics was kept. Overall, this is the first study to show the pH-sensitive properties of PI and one that may be useful for oral delivery of the probiotics.
Keywords
Probiotics; oral delivery; pH-sensitive tablet; phthalyl inulin;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Petrovsky N, Cooper PD. 2015. Advax, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety. Vaccine 33: 5920-5926.   DOI
2 Oliveira RPD, Perego P, de Oliveira MN, Converti A. 2012. Effect of inulin on the growth and metabolism of a probiotic strain of Lactobacillus rhamnosus in co-culture with Streptococcus thermophilus. Lwt-Food Sci. Technol. 47: 358-363.   DOI
3 Im ran S, Gillis RB, Kok MS, Harding SE, Adam s GG. 2012. Application and use of Inulin as a tool for therapeutic drug delivery. Biotechnol. Genet. Eng.Rev. 28: 33-45.   DOI
4 Akhgari A, Farahmand F, Afrasiabi Garekani H, Sadeghi F, Vandamme TF. 2006. Permeability and swelling studies on free films containing inulin in combination with different polymethacrylates aimed for colonic drug delivery. Eur. J. Pharm. Sci. 28: 307-314.   DOI
5 Van den Mooter G, Vervoort L, Kinget R. 2003. Characterization of methacrylated inulin hydrogels designed for colon targeting: In vitro release of BSA. Pharm. Res. 20: 303-307.   DOI
6 Castelli F, Sarpietro MG, Micieli D, Ottimo S, Pitarresi G, Tripodo G, et al. 2008. Differential scanning calorimetry study on drug release from an inulin-based hydrogel and its interaction with a biomembrane model: pH and loading effect. Eur. J. Pharm. Sci. 35: 76-85.   DOI
7 Calinescu C, Mulhbacher J, Nadeau E, Fairbrother JM, Mateescu MA. 2005. Carboxymethyl high amylose starch (CM-HAS) as excipient for Escherichia coli oral formulations. Eur. J. Pharm. Biopharm. 60: 53-60.   DOI
8 Sahu A, Bora U, Kasoju N, Goswami P. 2008. Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells. Acta Biomater. 4: 1752-1761.   DOI
9 Lian WC, Hsiao HC, Chou CC. 2003. Viability of microencapsulated bifidobacteria in simulated gastric juice and bile solution. Int. J. Food Microbiol. 86: 293-301.   DOI
10 Debas HT. 1977. Regulation of gastric acid secretion. Fed. Proc. 36: 1933-1937.
11 Dowarah R, Verma AK, Agarwal N. 2017. The use of Lactobacillus as an alternative of antibiotic growth promoters in pigs: a review. Anim. Nutr. 3: 1-6.   DOI
12 Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in't Veld JH. 1998. Overview of gut flora and probiotics. Int. J. Food Microbiol. 41: 85-101.   DOI
13 Masco L, Crockaert C, Van Hoorde K, Swings J, Huys G. 2007. In vitro assessment of the gastrointestinal transit tolerance of taxonomic reference strains from human origin and probiotic product isolates of Bifidobacterium. J. Dairy Sci. 90: 3572-3578.   DOI
14 Sorensen TL, Blom M, Monnet DL, Frimodt-Moller N, Poulsen RL, Espersen F. 2001. Transient intestinal carriage after ingestion of antibiotic-resistant Enterococcus faecium from chicken and pork. N. Engl. J. Med. 345: 1161-1166.   DOI
15 Anal AK, Singh H. 2007. Recent advances in microencapsulation of probiotics for industrial applications and targeted delivery. Trends Food Sci. Tech. 18: 240-251.   DOI
16 Kechagia M, Basoulis D, Konstantopoulou S, Dimitriadi D, Gyftopoulou K, Skarmoutsou N, et al. 2013. Health benefits of probiotics: a review. ISRN Nutr. 2013: 481651.
17 Forkus B, Ritter S, Vlysidis M, Geldart K, Kaznessis YN. 2017. Antimicrobial probiotics reduce salmonella enterica in turkey gastrointestinal tracts. Sci. Rep. 7: 40695.   DOI
18 Doyle MP, Erickson MC. 2006. Reducing the carriage of foodborne pathogens in livestock and poultry. Poult. Sci. 85: 960-973.   DOI
19 Lee JY, Han GG, Choi J, Jin GD, Kang SK, Chae BJ, et al. 2017. Pan-genomic approaches in lactobacillus reuteri as a porcine probiotic: investigation of host adaptation and antipathogenic activity. Microb. Ecol. 74: 709-721.   DOI
20 Sinha VR, Kumria R. 2001. Polysaccharides in colon-specific drug delivery. Int. J. Pharm. 224: 19-38.   DOI
21 Akhgari A. 2015. Role of polysaccharides in colon-specific drug delivery. Jundishapur. J. Nat. Pharm. Prod. 10: e30388.   DOI
22 Ravi V, Kum ar STMP. 2008. Influence of natural polym er coating on novel colon targeting drug delivery system. J. Mater. Sci. Mater. Med. 19: 2131-2136.   DOI
23 Papadimitriou K, Zoumpopoulou G, Foligne B, Alexandraki V, Kazou M, Pot B, et al. 2015. Discovering probiotic microorganisms: in vitro, in vivo, genetic and omics approaches. Front. Microbiol. 6: 58.   DOI
24 Cheng G, Hao H, Xie S, Wang X, Dai M, Huang L, et al. 2014. Antibiotic alternatives: the substitution of antibiotics in animal husbandry? Front. Microbiol. 5: 217.   DOI
25 Petros RA, DeSimone JM. 2010. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9: 615-627.   DOI
26 Jiang T, Li HS, Han GG, Singh B, Kang SK, Bok JD, et al. 2017. Oral delivery of probiotics in poultry using pH-sensitive tablets. J. Microbiol. Biotechnol. 27: 739-746.   DOI
27 Kim W-S, Lee J-Y, Singh B, Maharjan S, Hong L, Lee S-M, et al. 2018. A new way of producing pediocin in Pediococcus acidilactici through intracellular stimulation by internalized inulin nanoparticles. Sci. Rep. 8: 5878.   DOI
28 Chavda H, Patel C. 2011. Effect of crosslinker concentration on characteristics of superporous hydrogel. Int. J. Pharm. Investig. 1: 17-21.   DOI
29 Solanki HK, Pawar DD, Shah DA, Prajapati VD, Jani GK, Mulla AM, et al. 2013. Development of microencapsulation delivery system for long-term preservation of probiotics as biotherapeutics agent. Biomed. Res. Int. 2013: 620719.
30 Collins JW LRR, Woodward MJ, Searle LE 2009. pp. 1123-1192. Application of Prebiotics and Probiotics in Livestock. Prebiotics and probiotics science and technology. Springer, BerlinHeideberg. Germany.
31 Yang XY, Wang YS, Huang X, Ma YF, Huang Y, Yang RC, et al. 2011. Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity. J. Mater. Chem. 21: 3448-3454.   DOI
32 Wang XQ, Zhang Q. 2012. pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs. Eur. J. Pharm. Biopharm. 82: 219-229.   DOI
33 Dai JD, Nagai T, Wang XQ, Zhang T, Meng M, Zhang Q. 2004. pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine A. Int. J. Pharm. 280: 229-240.   DOI
34 Liu L, Yao WD, Rao YF, Lu XY, Gao JQ. 2017. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms. Drug Deliv. 24: 569-581.   DOI
35 Singh B, Maharjan S, Jiang T, Kang SK, Choi YJ, Cho CS. 2015. Attuning hydroxypropyl methylcellulose phthalate to oral delivery vehicle for effective and selective delivery of protein vaccine in ileum. Biomaterials 59: 144-159.   DOI
36 Fukui E, Miyamura N, Kobayashi M. 2001. An in vitro investigation of the suitability of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydrophobic additives in the outer shell for colon targeting. J. Control. Release 70: 97-107.   DOI
37 Lee HB, Yoon SY, Singh B, Oh SH, Cui LH, Yan CG, et al. 2018. Oral immunization of FMDV vaccine using pH-sensitive and mucoadhesive thiolated cellulose acetate phthalate microparticles. Tissue Eng. Regen. Med. 15: 1-11.   DOI
38 Mensink MA, Frijlink HW, Maarschalk KV, Hinrichs WLJ. 2015. Inulin, a flexible oligosaccharide I: review of its physicochemical characteristics. Carbohydr. Polym. 130: 405-419.   DOI
39 Tremaroli V, Backhed F. 2012. Functional interactions between the gut microbiota and host metabolism. Nature 489: 242-249.   DOI
40 Seifert S, Watzl B. 2007. Inulin and oligofructose: review of experimental data on immune modulation. J. Nutr. 137: 2563s-2567s.   DOI
41 Skwarczynski M. 2017. Inulin: a new adjuvant with unknown mode of action. EBIO Medicine 15: 8-9.