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Recent Advances in Drug Delivery and Formulation

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ISSN (Print): 2667-3878
ISSN (Online): 2667-3886

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Research Article

In Vitro Development of Enteric-Coated Tablets of the Probiotic Lactobacillus fermentum LF-G89: A Possible Approach to Intestinal Colonization

Author(s): Paola Spínello, Pamela do Nascimento, Verônica Cristina da Silveira, Tatiana Staudt, Hamid Omidian, Ana Caroline Tissiani and Charise Dallazem Bertol*

Volume 18, Issue 2, 2024

Published on: 24 April, 2024

Page: [131 - 137] Pages: 7

DOI: 10.2174/0126673878286133240418114629

Price: $65

Abstract

Background: Probiotics must be able to withstand the demanding environment of the gastrointestinal system to adhere to the intestinal epithelium, promoting health benefits. The use of probiotics can prevent or attenuate the effects of dysbiosis that have a deleterious effect on health, promoting anti-inflammatory, immunomodulatory, and antioxidant effects.

Objective: The aim of the study was to prepare tablets containing Lactobacillus fermentum LF-G89 coated with 20% Acryl-Eze II® or Opadry® enteric polymers.

Methods: Tablet dissolution was evaluated under acidic and basic pH conditions, and aliquots of the dissolution medium were plated to count the Colony-forming Units (CFU). The free probiotic's tolerance to pH levels of 1.0, 2.0, 3.0, and 4.0, as well as to pepsin, pancreatin, and bile salts, was assessed.

Results: The probiotic was released from tablets coated after they withstood the pH 1.2 acid stage for 45 minutes. The release was higher with the Acry-Eze II® polymer in the basic stage. The amount of CFU of free probiotics at pH 1.0 to 4.0 as well as pepsin reduced over time, indicating cell death. Conversely, the CFU over time with pancreatin and bile salts increased, demonstrating the resistance of L. fermentum to these conditions due to hydrolases.

Conclusion: Both coating polymers were able to withstand the acid step, likely ensuring the release of the probiotic in the small intestine, promoting colonization. Coating with enteric material is a simple and effective process to increase the survival of probiotics, offering a promising alternative to mitigate the negative effects of the dysbiosis process.

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Graphical Abstract

[1]
Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014; 11(8): 506-14.
[http://dx.doi.org/10.1038/nrgastro.2014.66] [PMID: 24912386]
[2]
Song D, Ibrahim S, Hayek S, Song D, Ibrahim S, Hayek S. Recent application of probiotics in food and agricultural science. Probiotics. London, United Kingdom: IntechOpen Ltd. 2012.
[http://dx.doi.org/10.5772/50121]
[3]
Evivie SE, Huo GC, Igene JO, Bian X. Some current applications, limitations and future perspectives of lactic acid bacteria as probiotics. Food Nutr Res 2017; 61(1): 1318034.
[http://dx.doi.org/10.1080/16546628.2017.1318034] [PMID: 28659729]
[4]
Kiousi DE, Kouroutzidou AZ, Neanidis K, Matthaios D, Pappa A, Galanis A. Evaluating the role of probiotics in the prevention and management of age-related diseases. Int J Mol Sci 2022; 23(7): 3628.
[http://dx.doi.org/10.3390/ijms23073628]
[5]
Yun B, Ryu S, Kang M, et al. Probiotic Lacticaseibacillus rhamnosus GG Increased Longevity and Resistance Against Foodborne Pathogens in Caenorhabditis elegans by Regulating MicroRNA miR-34. Front Cell Infect Microbiol 2022; 11: 819328.
[http://dx.doi.org/10.3389/fcimb.2021.819328] [PMID: 35127565]
[6]
Boyajian JL, Ghebretatios M, Schaly S, Islam P, Prakash S. Microbiome and human aging: Probiotic and prebiotic potentials in longevity, skin health and cellular senescence. Nutrients 2021; 13(12): 4550.
[http://dx.doi.org/10.3390/nu13124550] [PMID: 34960102]
[7]
Lee K, Kim J, Park SD, Shim JJ, Lee JL. Lactobacillus plantarum HY7715 ameliorates sarcopenia by improving skeletal muscle mass and function in aged Balb/c Mice. Int J Mol Sci 2021; 22(18): 10023.
[http://dx.doi.org/10.3390/ijms221810023] [PMID: 34576187]
[8]
Jemimah S, Chabib CMM, Hadjileontiadis L, AlShehhi A. Gut microbiome dysbiosis in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis. PLoS One 2023; 18(5): e0285346.
[http://dx.doi.org/10.1371/journal.pone.0285346] [PMID: 37224131]
[9]
Giovannini MG, Lana D, Traini C, Vannucchi MG. The microbiota–gut–brain axis and alzheimer disease. From dysbiosis to neurodegeneration: Focus on the central nervous system glial cells. J Clin Med 2021; 10: 2358.
[10]
Janeiro MH, Ramírez MJ, Solas M. Dysbiosis and alzheimer’s disease: Cause or treatment opportunity? Cell Mol Neurobiol 2022; 42: 377-87.
[11]
Sharma VK, Singh TG, Garg N, Dhiman S, Gupta S, Rahman MH. Dysbiosis and alzheimer’s disease: A role for chronic stress? Biomolecules 2021; 11(5): 678.
[http://dx.doi.org/10.3390/biom11050678]
[12]
Du Y, Gao Y, Zeng B, Fan X, Yang D, Yang M. Effects of anti-aging interventions on intestinal microbiota. Gut Microbes 2021; 13(1): 1994835.
[http://dx.doi.org/10.1080/19490976.2021.1994835] [PMID: 34743658]
[13]
dos Reis SA, da Conceição LL, Siqueira NP, Rosa DD, da Silva LL, Peluzio MCG. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res 2017; 37: 1-19.
[http://dx.doi.org/10.1016/j.nutres.2016.11.009] [PMID: 28215310]
[14]
Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J 2015; 8(1): 4.
[http://dx.doi.org/10.1186/s40413-015-0055-2] [PMID: 25628773]
[15]
Scholz-Ahrens KE, Adolphi B, Rochat F, et al. Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats — impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over. NFS J 2016; 3: 41-50.
[http://dx.doi.org/10.1016/j.nfs.2016.03.001]
[16]
Amara AA, Shibl A. Role of probiotics in health improvement, infection control and disease treatment and management. Saudi Pharm J 2015; 23(2): 107-14.
[http://dx.doi.org/10.1016/j.jsps.2013.07.001] [PMID: 25972729]
[17]
Bielecka M, Biedrzycka E, Majkowska A. Selection of probiotics and prebiotics for synbiotics and confirmation of their in vivo effectiveness. Food Res Int 2002; 35(2-3): 125-31.
[http://dx.doi.org/10.1016/S0963-9969(01)00173-9]
[18]
Cazorla SI, Maldonado-Galdeano C, Weill R, De Paula J, Perdigón GDV. Oral administration of probiotics increases paneth cells and intestinal antimicrobial activity. Front Microbiol 2018; 9: 736.
[http://dx.doi.org/10.3389/fmicb.2018.00736] [PMID: 29713315]
[19]
Kusada H, Arita M, Tohno M, Tamaki H. Bile salt hydrolase degrades β-lactam antibiotics and confers antibiotic resistance on Lactobacillus paragasseri. Front Microbiol 2022; 13: 858263.
[http://dx.doi.org/10.3389/fmicb.2022.858263] [PMID: 35733973]
[20]
Vandenplas Y, Huys G, Daube G. Probiotics: An update. J Pediatr (Rio J) 2015; 91(1): 6-21.
[http://dx.doi.org/10.1016/j.jped.2014.08.005] [PMID: 25458874]
[21]
Han S, Lu Y, Xie J, et al. Probiotic gastrointestinal transit and colonization after oral administration: A long journey. Front Cell Infect Microbiol 2021; 11: 609722.
[http://dx.doi.org/10.3389/fcimb.2021.609722] [PMID: 33791234]
[22]
Luo Y, De Souza C, Ramachandran M, et al. Precise oral delivery systems for probiotics: A review. J Control Release 2022; 352: 371-84.
[http://dx.doi.org/10.1016/j.jconrel.2022.10.030] [PMID: 36309096]
[23]
Lemos Junior WJF, Guerra AF, Tarrah A, et al. Safety and stability of two potentially probiotic Lactobacillus strains after in vitro gastrointestinal transit. Probiotics Antimicrob Proteins 2020; 12(2): 657-66.
[http://dx.doi.org/10.1007/s12602-019-09565-2] [PMID: 31214943]
[24]
Kechagia M, Basoulis D, Konstantopoulou S, et al. Health benefits of probiotics: A review. ISRN Nutr 2013; 2013: 1-7.
[http://dx.doi.org/10.5402/2013/481651] [PMID: 24959545]
[25]
Brizuela MA, Serrano P, Pérez Y. Studies on probiotics properties of two Lactobacillus strains. Braz Arch Biol Technol 2001; 44(1): 95-9.
[http://dx.doi.org/10.1590/S1516-89132001000100013]
[26]
Bushra R, Shoaib MH, Aslam N, Mehmood ZA, Hashmat D, Bushra R. Enteric coating of ibuprofen tablets (200 mg) using an aqueous dispersion system. Braz J Pharm Sci 2010; 46(1): 99-107.
[http://dx.doi.org/10.1590/S1984-82502010000100011]
[27]
Chaurasia S, Mishra B. Synthetic polymers as biomaterials for the treatment of colon diseases. Advanced drug delivery systems for colonic disorders. Advanced drug delivery systems for colonic disorders. Cambridge, Massachusetts: Academic Press 2024; pp. 95-130.
[http://dx.doi.org/10.1016/B978-0-443-14044-0.00018-1]
[28]
Klayraung S, Okonogi S. Antibacterial and antioxidant activities of acid and bile resistant strains of Lactobacillus fermentum isolated from miang. Braz J Microbiol 2009; 40(4): 757-66.
[http://dx.doi.org/10.1590/S1517-83822009000400005] [PMID: 24031422]
[29]
De Man JC, Rogosa M, Sharpe ME. A medium for the cultivation of Lactobacilli. J Appl Bacteriol 1960; 23(1): 130-5.
[http://dx.doi.org/10.1111/j.1365-2672.1960.tb00188.x]
[30]
Reque EF, Pandey A, Franco SG, Soccol CR. Isolation, identification and physiological study of Lactobacillus fermentum LPB for use as probiotic in chickens. Braz J Microbiol 2000; 31(4): 303-7.
[http://dx.doi.org/10.1590/S1517-83822000000400012]
[31]
Guimarães RR, Vendramini ALA, Santos AC, Leite SGF, Miguel MAL. Development of probiotic beads similar to fish eggs. J Funct Foods 2013; 5(2): 968-73.
[http://dx.doi.org/10.1016/j.jff.2013.01.002]
[32]
National Health Surveillance Agency - Anvisa. The Brazilian Pharmacopoeia. 2019. Available From: https://www.gov.br/anvisa/pt-br/assuntos/farmacopeia/farmacopeia-brasileira
[33]
Conway PL, Gorbach SL, Goldin BR. Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells. J Dairy Sci 1987; 70(1): 1-12.
[http://dx.doi.org/10.3168/jds.S0022-0302(87)79974-3] [PMID: 3106442]
[34]
Maragkoudakis PA, Zoumpopoulou G, Miaris C, Kalantzopoulos G, Pot B, Tsakalidou E. Probiotic potential of Lactobacillus strains isolated from dairy products. Int Dairy J 2006; 16(3): 189-99.
[http://dx.doi.org/10.1016/j.idairyj.2005.02.009]
[35]
Charteris WP, Kelly PM, Morelli L, Collins JK. Development and application of an in vitro methodology to determine the transit tolerance of potentially probiotic Lactobacillus and Bifidobacterium species in the upper human gastrointestinal tract. J Appl Microbiol 1998; 84(5): 759-68.
[http://dx.doi.org/10.1046/j.1365-2672.1998.00407.x] [PMID: 9674129]
[36]
Dashkevicz MP, Feighner SD. Development of a differential medium for bile salt hydrolase-active Lactobacillus spp. Appl Environ Microbiol 1989; 55(1): 11-6.
[http://dx.doi.org/10.1128/aem.55.1.11-16.1989] [PMID: 2705765]
[37]
Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis 2015; 60 (Suppl. 2): S129-34.
[http://dx.doi.org/10.1093/cid/civ085] [PMID: 25922398]
[38]
Yang ZZ, Zhang YQ, Wang ZZ, Wu K, Lou JN, Qi XR. Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration. Int J Pharm 2013; 452(1-2): 344-54.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.009] [PMID: 23680731]
[39]
Zhang P, Iqbal S, Deng R, et al. Impact of elderly gastrointestinal alterations on gastric emptying and enzymatic hydrolysis of skim milk: An in vitro study using a dynamic stomach system. Food Chem 2023; 402: 134365.
[http://dx.doi.org/10.1016/j.foodchem.2022.134365] [PMID: 36179522]
[40]
Hwang YH, Park S, Paik JW, Chae SW, Kim DH, Jeong DG. Efficacy and safety of Lactobacillus Plantarum C29-fermented soybean (dw2009) in individuals with mild cognitive impairment: A 12-week, multi-center, randomized, double-blind, placebo-controlled clinical trial. Nutrients 2019; 11(2): 305.
[41]
Aljumaah MR, Bhatia U, Roach J, Gunstad J, Azcarate Peril MA. The gut microbiome, mild cognitive impairment, and probiotics: A randomized clinical trial in middle-aged and older adults. Clin Nutr 2022; 41(11): 2565-76.
[http://dx.doi.org/10.1016/j.clnu.2022.09.012] [PMID: 36228569]
[42]
Gareau MG. Cognitive function and the microbiome. Int Rev Neurobiol 2016; 131: 227-46.
[http://dx.doi.org/10.1016/bs.irn.2016.08.001] [PMID: 27793221]
[43]
Östlund-Lagerström L, Kihlgren A, Repsilber D, Björkstén B, Brummer RJ, Schoultz I. Probiotic administration among free-living older adults: A double blinded, randomized, placebo-controlled clinical trial. Nutr J 2015; 15(1): 80.
[http://dx.doi.org/10.1186/s12937-016-0198-1] [PMID: 27612653]
[44]
Šola KF, Vladimir-Knežević S, Hrabač P, Mucalo I, Saso L, Verbanac D. The effect of multistrain probiotics on functional constipation in the elderly: A randomized controlled trial. Eur J Clin Nutr 2022; 76(12): 1675-81.
[45]
Pu F, Guo Y, Li M, et al. Yogurt supplemented with probiotics can protect the healthy elderly from respiratory infections: A randomized controlled open-label trial. Clin Interv Aging 2017; 12: 1223-31.
[http://dx.doi.org/10.2147/CIA.S141518] [PMID: 28848330]
[46]
Lei M, Hua LM, Wang DW. The effect of probiotic treatment on elderly patients with distal radius fracture: A prospective double-blind, placebo-controlled randomised clinical trial. Benef Microbes 2016; 7(5): 631-7.
[http://dx.doi.org/10.3920/BM2016.0067]
[47]
Sanborn V, Azcarate-Peril MA, Updegraff J, Manderino LM, Gunstad J. A randomized clinical trial examining the impact of LGG probiotic supplementation on psychological status in middle-aged and older adults. Contemp Clin Trials Commun 2018; 12: 192-7.
[http://dx.doi.org/10.1016/j.conctc.2018.11.006] [PMID: 30511028]
[48]
Cicero AFG, Fogacci F, Bove M, Giovannini M, Borghi C. Impact of a short-term synbiotic supplementation on metabolic syndrome and systemic inflammation in elderly patients: A randomized placebo-controlled clinical trial. Eur J Nutr 2021; 60(2): 655-63.
[http://dx.doi.org/10.1007/s00394-020-02271-8] [PMID: 32417946]
[49]
Amaral Silva D, Davies NM, Doschak MR, Al-Gousous J, Bou-Chacra N, Löbenberg R. Mechanistic understanding of underperforming enteric coated products: Opportunities to add clinical relevance to the dissolution test. J Control Release 2020; 325: 323-34.
[http://dx.doi.org/10.1016/j.jconrel.2020.06.031] [PMID: 32649973]
[50]
Villena MJM, Lara-Villoslada F, Martínez MAR, Hernández MEM. Development of gastro-resistant tablets for the protection and intestinal delivery of Lactobacillus fermentum CECT 5716. Int J Pharm 2015; 487(1-2): 314-9.
[http://dx.doi.org/10.1016/j.ijpharm.2015.03.078] [PMID: 25843758]
[51]
Rodriguez MTS, Urbano HC, de los Ríos DM, Villoslada FL, Martínez MAR, Hernández MEM. Evaluation of viability of Lactobacillus fermentum CECT 5716 in gelatin and gastroresistant capsules. J Pharm Pharmacol 2016; 4(8): 4.
[52]
Liao N, Luo B, Gao J, et al. Oligosaccharides as co-encapsulating agents: Effect on oral Lactobacillus fermentum survival in a simulated gastrointestinal tract. Biotechnol Lett 2019; 41(2): 263-72.
[http://dx.doi.org/10.1007/s10529-018-02634-6] [PMID: 30535881]
[53]
Allouche R, Dupont S, Charriau A, Gervais P, Beney L, Chambin O. Optimized tableting for extremely oxygen-sensitive probiotics using direct compression. Int J Pharm 2018; 538(1-2): 14-20.
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.010] [PMID: 29307771]
[54]
Aulton ME. Delineamento de formas farmacêuticas. (2nd ed.), Porto Alegre: Artmed 2005.
[55]
Chan ES, Zhang Z. Encapsulation of probiotic bacteria Lactobacillus acidophilus by direct compression. Food Bioprod Process 2002; 80(2): 78-82.
[http://dx.doi.org/10.1205/09603080252938708]
[56]
Chan ES, Zhang Z. Bioencapsulation by compression coating of probiotic bacteria for their protection in an acidic medium. Process Biochem 2005; 40(10): 3346-51.
[http://dx.doi.org/10.1016/j.procbio.2005.03.001]
[57]
Kumar R, Rajkumar H, Kumar M, et al. Molecular cloning, characterization and heterologous expression of bile salt hydrolase (Bsh) from Lactobacillus fermentum NCDO394. Mol Biol Rep 2013; 40(8): 5057-66.
[http://dx.doi.org/10.1007/s11033-013-2607-2] [PMID: 23673477]
[58]
Kumar R, Grover S, Batish VK. Hypocholesterolaemic effect of dietary inclusion of two putative probiotic bile salt hydrolase-producing Lactobacillus plantarum strains in Sprague–Dawley rats. Br J Nutr 2011; 105(4): 561-73.
[http://dx.doi.org/10.1017/S0007114510003740] [PMID: 20923582]
[59]
Ontario L. Food and Agriculture Organization of the United Nations World Health Organization. 2024. Available From: https://www.fao.org/home/en
[60]
Liserre AM, Ré MI, Franco BDGM. Microencapsulation of Bifidobacterium animalis subsp. lactis and Lactobacillus acidophilus in cocoa butter using spray chilling technology. Braz J Microbiol 2013; 44(3): 777-83.

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