Abstract
ZnO is a commonly used antibiotic alternative in managing post-weaning piglet diarrhea. However, a major struggle faced in the industry is in being able to taper the amount of ZnO given to piglets to curb downstream environmental harm when it is excreted. To meet these demands, this research focuses on ZnO encapsulation, which offers an opportunity to increase ZnO targetability and reduce premature loss. In this research, ZnO is also delivered as nanoparticles, which has benefits for improving the antibacterial action against enterotoxigenic E. coli—the most common pathogen of post-weaning piglet diarrhea. ZnO nanoparticles were suspended in an oil-based core encased in a EUDRAGIT® L100 shell (core–shell ZnO microparticles) were fabricated and studied for their ZnO release profile in both simulated conditions and digestive fluid conditions. Digestive fluid release studies demonstrate 30% premature ZnO release compared to simulated conditions that showed over 50% premature ZnO release (p < 0.001) prior to reaching the target location. The digestive studies highlight how the interactions within the piglet digestive fluids make it difficult to reproduce in simulated studies and benefits as a step-up study to better reflect on the complexities of the piglet gut. Finally, we assessed the antibacterial activity of the core–shell ZnO microparticles against enterotoxigenic E. coli for combating post-weaning diarrhea, demonstrating the ability for the microparticles to meet MIC and sustain it within the target location. By the WST-8 assay method, we also report the MIC for ZnO nanoparticles against enterotoxigenic E. coli to be 0.125 mg/mL.
Similar content being viewed by others
Availability of data and materials
Not applicable.
Code availability
Not applicable.
References
Azam A, Ahmed AS, Oves M, Khan MS, Habib SS, Memic A (2012) Antimicrobial activity of metal oxide nanoparticles against Gram-positive and Gram-negative bacteria: a comparative study. Int J Nanomed 7:6003–6009
Baek S, Joo SH, Toborek M (2019) Treatment of antibiotic-resistant bacteria by encapsulation of ZnO nanoparticles in an alginate biopolymer: Insights into treatment mechanisms. J Hazard Mater 373:122–130
Barreto MSR, Andrade CT, da Silva L, Cabral LM, FlosiPaschoalin VM, Del Aguila EM (2017) In vitro physiological and antibacterial characterization of ZnO nanoparticle composites in simulated porcine gastric and enteric fluids. BMC Vet Res 13:181–190
Braia M, Tubio G, Nerli B, Loh W, Romanini D (2012) Analysis of the interactions between Eudragit(R) L100 and porcine pancreatic trypsin by calorimetric techniques. Int J Biol Macromol 50:180–186
Byun YJ, Lee CY, Kim MH, Jung DY, Han JH, Jang I, Song YM, Park BC (2017) Effects of dietary supplementation of a lipid-coated zinc oxide product on the fecal consistency, growth, and morphology of the intestinal mucosa of weanling pigs. J Anim Sci Technol 59:29–34
de Souza RC, Haberbeck LU, Riella HG, Ribeiro DHB, Carciofi BAM (2019) Antibacterial activity of zinc oxide nanoparticles synthesized by solochemical process. Braz J Chem Eng 36:885–893
Kim C, Wilkins K, Bowers M, Wynn C, Ndegwa E (2018) Influence of pH and temperature on growth characteristics of leading foodborne pathogens in a laboratory medium and select food beverages. Austin Food Sci 3:1–8
Kwon CH, Lee CY, Han SJ, Kim SJ, Park BC, Jang I, Han JH (2014) Effects of dietary supplementation of lipid-encapsulated zinc oxide on colibacillosis, growth and intestinal morphology in weaned piglets challenged with enterotoxigenic Escherichia coli. Anim Sci J 85:805–813
Long L, Chen J, Zhang Y, Liang X, Ni H, Zhang B, Yin Y (2017) Comparison of porous and nano zinc oxide for replacing high-dose dietary regular zinc oxide in weaning piglets. PLoS ONE 12:1–14
Minekus M, Alminger M, Alvito P et al (2014) A standardised static in vitro digestion method suitable for food—an international consensus. Food Funct 5:1113–1124
Ouyang Z, Ren P, Zhen D, Huang L, Wei T, Yang C, Kong X, Yin Y, He S, He Q (2021) Hydrothermal synthesis of a new porous zinc oxide and its antimicrobial evaluation in weanling piglets. Livest Sci 248:1–7
Padmavathy N, Vijayaraghavan R (2008) Enhanced bioactivity of ZnO nanoparticles-an antimicrobial study. Sci Technol Adv Mater 9:1–7
Pasquet J, Chevalier Y, Pelletier J, Couval A, Bouvier D, Bolzinger MA (2014) The contribution of zinc ions to the antimicrobial activity of zinc oxide. Colloids Surf A Physiochem Eng Asp 457:263–274
Pati R, Mehta RK, Mohanty S, Padhi A, Sengupta M, Vaseeharan B, Goswami C, Sonawane A (2014) Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages. Nanomedicine 10:1195–1208
Premanathan M, Karthikeyan K, Jeyasubramanian K, Manivannan G (2011) Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomedicine 7:184–192
Rizi K, Green RJ, Donaldson M, Williams AC (2011) Production of pH-responsive microparticles by spray drying: investigation of experimental parameter effects on morphological and release properties. J Pharm Sci 100:566–579
Roselli M, Finamore A, Garaguso I, Britti M, Mengheri E (2003) Zinc oxide protects cultured enterocytes from the damage induced by Escherichia coli. J Nutr 133:4077–4082
Saliani M, Jalal R, KafshdareGoharshadi E (2014) Effects of pH and temperature on antibacterial activity of zinc oxide nanofluid against Escherichia coli O157: H7 and Staphylococcus aureus. Jundishapur J Microbiol 8:1–6
Sánchez-Clemente R, Igeño MI, Población AG, Guijo MI, Merchán F, Blasco R (2018) Study of pH changes in media during bacterial growth of several environmental strains. Proceedings 2:1297–1302
Shankar S, Rhim JW (2019) Effect of Zn salts and hydrolyzing agents on the morphology and antibacterial activity of zinc oxide nanoparticles. Environ Chem Lett 17:1105–1109
Shen J, Chen Y, Wang Z, Zhou A, He M, Mao L, Zou H, Peng Q, Zue B, Wang L, Zhang X, Wu S, Lv Y (2014) Coated zinc oxide improves intestinal immunity function and regulates microbiota composition in weaned piglets. Br J Nutr 111:2123–2134
Shepard KB, Adam MS, Morgen MM, Mudie DM, Regan DT, Baumann JM, Vodak DT (2020) Impact of process parameters on particle morphology and filament formation in spray dried Eudragit L100 polymer. Powder Technol 362:221–230
Shishir MRI, Xie L, Sun C, Zheng X, Chen W (2018) Advances in micro and nano-encapsulation of bioactive compounds using biopolymer and lipid-based transporters. Trends Food Sci Technol 78:34–60
Siddiqi KS, Ur Rahman A, Tajuddin HA (2018) Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res Lett 13:141–154
Sinha R, Sahoo NR, Shrivastava K, Kumar P, Qureshi S, De UK, Kumar A, Kumar G, Bhushan B (2019) Resistance to ETEC F4/F18-mediated piglet diarrhoea: opening the gene black box. Trop Anim Health Prod 51:1307–1320
Sol C, Castillejos L, López-Vergé S, Gasa J (2017) Prediction of the digestibility and energy contents of non-conventional by-products for pigs from their chemical composition and in vitro digestibility. Anim Feed Sci Technol 234:237–243
Srivastava A, Gowda DV, Madhunapantula SV, Siddaramaiah, (2016) Development and efficacy assessment of an enteric coated porous tablet loaded with F4 fimbriae for oral vaccination of piglets against F4+ entertoxigenic Escherichia coli infections. Curr Drug Deliv 13:121–130
Sun Y, Kim SW (2017) Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea. Anim Nutr 3:322–330
Temiz U, Öztürk E (2018) Encapsulation methods and use in animal nutrition. Selcuk J Agric Food Sci 32:624–631
Tsukatani T, Suenaga H, Shiga M, Noguchi K, Ishiyama M, Ezoe T, Matsumoto K (2012) Comparison of the WST-8 colorimetric method and the CLSI broth microdilution method for susceptibility testing against drug-resistant bacteria. J Microbiol Methods 90:160–166
Turchiuli C, Jimenez Munguia MT, Hernandez Sanchez M, Cortes Ferre H, Dumoulin E (2014) Use of different supports for oil encapsulation in powder by spray drying. Powder Technol 255:103–108
Upadhaya SD, Kim YM, Lee KY, Kim IH (2018) Use of protected zinc oxide in lower doses in weaned pigs in substitution for the conventional high dose zinc oxide. Anim Feed Sci Technol 240:1–10
Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, Teillant A, Laxminarayan R (2015) Global trends in antimicrobial use in food animals. Proc Natl Acad Sci USA 112:5649–5654
Wang Q, Gong J, Huang X, Yu H, Xue F (2009) In vitro evaluation of the activity of microencapsulated carvacrol against Escherichia coli with K88 pili. J Appl Microbiol 107:1781–1788
Wang C, Liu LL, Zhang AT, Xie P, Lu JJ, Zou XT (2012) Antibacterial effects of zinc oxide nanoparticles on Escherichia coli K88. Afr J Biotechnol 11:10248–10254
Wang C, Zhang L, Su W, Ying Z, He J, Zhang L, Zhong X, Wang T (2017) Zinc oxide nanoparticles as a substitute for zinc oxide or colistin sulfate: effects on growth, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets. PLoS ONE 12:1–14
Wang C, Zhang L, Ying Z, He J, Zhou L, Zhang L, Zhong X, Wang T (2018) Effects of dietary zinc oxide nanoparticles on growth, diarrhea, mineral deposition, intestinal morphology, and barrier of weaned piglets. Biol Trace Elem Res 185:364–374
Yousef JM, Danial EN (2012) In vitro antibacterial activity and minimum inhibitory concentration of zinc oxide and nano-particle zinc oxide against pathogenic strains. Int J Health Sci 2:38–42
Zhang Y, Wang QC, Yu H, Zhu J, de Lange K, Yin Y, Wang Q, Gong J (2016) Evaluation of alginate-whey protein microcapsules for intestinal delivery of lipophilic compounds in pigs. J Sci Food Agric 96:2674–2681
Zhu C, Ye JL, Yang J, Yang KM, Chen Z, Liang R, Wu XJ, Wang L, Jiang ZY (2017) Differential expression of intestinal ion transporters and water channel aquaporins in young piglets challenged with enterotoxigenic Escherichia coli K88. J Anim Sci 95:5240–5252
Funding
University Collaborative Research Program, Natural Sciences and Engineering Research Council of Canada Discovery Grant (RGPIN-2019-06094) awarded to Dr. Song Liu, Research Manitoba Master’s Studentship awarded to Lucy Wang.
Author information
Authors and Affiliations
Contributions
Funding acquisition by SL and CY; conceptualization and experimental design by LW, SL, and CY; data collection by LW; manuscript preparation and editing by LW, SL, and CY.
Corresponding authors
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to declare.
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wang, L.L., Yang, C. & Liu, S. Development and antibacterial activity of zinc oxide nanoparticles encapsulated in core–shell microparticles for managing enterotoxigenic Escherichia coli-related post-weaning diarrhea. Appl Nanosci 12, 1449–1458 (2022). https://doi.org/10.1007/s13204-021-02303-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13204-021-02303-7