{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:58:03Z","timestamp":1787065083335,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department for Environment, Food and Rural Affairs","award":["SE3246"],"award-info":[{"award-number":["SE3246"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally, but oral delivery is highly advantageous for the immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in phosphate-buffered saline (PBS), containing Tween\u00ae 80, with and without the addition of mannitol or trehalose. Samples were frozen at \u221220 \u00b0C, freeze-dried and the lyophilised powders were compressed to produce BCG\u2013Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in simulated intestinal fluid (SIF) within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.<\/jats:p>","DOI":"10.3390\/pharmaceutics11060270","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T11:39:47Z","timestamp":1560166787000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro Evaluation of Eudragit Matrices for Oral Delivery of BCG Vaccine to Animals"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-6668","authenticated-orcid":false,"given":"Imran","family":"Saleem","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan G. A.","family":"Coombes","sequence":"additional","affiliation":[{"name":"Pharmacy Australia Centre of Excellence, University of Queensland, School of Pharmacy, 20 Cornwall Street, Woolloongaba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-8069","authenticated-orcid":false,"given":"Mark A.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Animal and Plant Health Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK"},{"name":"School of Veterinary Medicine, University of Surrey, VSM Building, Daphne Jackson Rd, Guildford GU2 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). Global Tuberculosis Report 2018, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1016\/j.vaccine.2012.02.018","article-title":"Bovine tuberculosis vaccine research: Historical perspectives and recent advances","volume":"30","author":"Waters","year":"2012","journal-title":"Vaccine"},{"key":"ref_3","unstructured":"World Health Organization (2017). Roadmap for Zoonotic Tuberculosis, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3389\/fvets.2018.00259","article-title":"Efficacy and Safety of BCG Vaccine for Control of Tuberculosis in Domestic Livestock and Wildlife","volume":"5","author":"Buddle","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.vaccine.2016.12.004","article-title":"Testing of a palatable bait and compatible vaccine carrier for the oral vaccination of European badgers (Meles meles) against tuberculosis","volume":"35","author":"Gowtage","year":"2017","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cvex.2018.01.006","article-title":"Overview of Drug Delivery Methods in Exotics, Including Their Anatomic and Physiologic Considerations","volume":"21","author":"Coutant","year":"2018","journal-title":"Vet. Clin. N. Am. Exot. Anim. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1517\/17425247.5.1.69","article-title":"Past and future evolution in colloidal drug delivery systems","volume":"5","author":"Boyd","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1517\/17425247.2012.717068","article-title":"Oral delivery of peptides and proteins using lipid-based drug delivery systems","volume":"9","author":"Li","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_9","first-page":"1847","article-title":"Bile salts-containing vesicles: Promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide\/protein-based therapeutics or vaccines","volume":"23","author":"Aburahma","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.1128\/IAI.66.12.5669-5676.1998","article-title":"Systemic and mucosal immune responses after intranasal administration of recombinant Mycobacterium bovis bacillus Calmette-Guerin expressing glutathione S-transferase from Schistosoma haematobium","volume":"66","author":"Kremer","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1476-8518-4-4","article-title":"Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults","volume":"4","author":"Pinho","year":"2006","journal-title":"J. Immune Based Ther. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1128\/IAI.74.4.2449-2452.2006","article-title":"Boosting of cellular immunity against Mycobacterium tuberculosis and modulation of skin cytokine responses in healthy human volunteers by Mycobacterium bovis BCG substrain Moreau Rio de Janeiro oral vaccine","volume":"74","author":"Cosgrove","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.rvsc.2004.07.007","article-title":"Improving protective efficacy of BCG vaccination for wildlife against bovine tuberculosis","volume":"78","author":"Skinner","year":"2005","journal-title":"Res. Vet. Sci."},{"key":"ref_14","first-page":"377","article-title":"Intraduodenal vaccination of brushtail possums with bacille Calmette-Guerin enhances immune responses and protection against Mycobacterium bovis infection","volume":"1","author":"Buddle","year":"1997","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1080\/02652040601034013","article-title":"Stabilizing effects of calcium alginate microspheres on Mycobacterium bovis BCG intended for oral vaccination","volume":"23","author":"Dobakhti","year":"2006","journal-title":"J. Microencapsul."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gormley, E., Ni Bhuachalla, D., O\u2019Keeffe, J., Murphy, D., Aldwell, F.E., Fitzsimons, T., Stanley, P., Tratalos, J.A., McGrath, G., and Fogarty, N. (2017). Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guerin (BCG) Vaccine Confers Protection against Tuberculosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0168851"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1128\/CVI.00392-08","article-title":"Humoral immune responses of white-tailed deer (Odocoileus virginianus) to Mycobacterium bovis BCG vaccination and experimental challenge with M. bovis","volume":"16","author":"Nol","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nugent, G., Yockney, I.J., Whitford, E.J., Cross, M.L., Aldwell, F.E., and Buddle, B.M. (2016). Field Trial of an Aerially-Distributed Tuberculosis Vaccine in a Low-Density Wildlife Population of Brushtail Possums (Trichosurus vulpecula). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167144"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ejps.2018.09.002","article-title":"The promoting effect of enteric materials on the oral absorption of larotaxel-loaded polymer-lipid hybrid nanoparticles","volume":"124","author":"Gou","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.carbpol.2018.06.107","article-title":"Colon-targeted dexamethasone microcrystals with pH-sensitive chitosan\/alginate\/Eudragit S multilayers for the treatment of inflammatory bowel disease","volume":"198","author":"Oshi","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijpharm.2017.10.013","article-title":"Thermostability of the coating, antigen and immunostimulator in an adjuvanted oral capsule vaccine formulation","volume":"534","author":"Longet","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2174\/1567201812999150727131119","article-title":"Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded With F4 Fimbriae for Oral Vaccination of Piglets against F4+ Escherichia coli Infections","volume":"13","author":"Srivastava","year":"2016","journal-title":"Curr. Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0378-5173(03)00068-1","article-title":"Optimization of a formulation containing viable lactic acid bacteria","volume":"256","author":"Stadler","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ejpb.2005.02.012","article-title":"Development of an enteric-coated formulation containing freeze-dried, viable recombinant Lactococcus lactis for the ileal mucosal delivery of human interleukin-10","volume":"60","author":"Huyghebaert","year":"2005","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/S0264-410X(99)00231-5","article-title":"Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine","volume":"17","author":"Levine","year":"1999","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1002\/jps.23997","article-title":"A laminated polymer film formulation for enteric delivery of live vaccine and probiotic bacteria","volume":"103","author":"Scherer","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/S0022-5347(17)32340-6","article-title":"Time-dependent aggregation of reconstituted BCG vaccine","volume":"152","author":"Ratliff","year":"1994","journal-title":"J. Urol."},{"key":"ref_28","first-page":"251","article-title":"Stabilisation of BCG vaccines","volume":"87","author":"Gheorghiu","year":"1996","journal-title":"Dev. Biol. Stand."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0092-1157(88)90025-X","article-title":"The stability and immunogenicity of a dispersed-grown freeze-dried Pasteur BCG vaccine","volume":"16","author":"Gheorghiu","year":"1988","journal-title":"J. Biol. Stand."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.2042-7158.1997.tb06143.x","article-title":"BCG: The Past, Present and Future of a Tuberculosis Vaccine","volume":"49","author":"Groves","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mimet.2006.05.016","article-title":"Breaking down the wall: Fractionation of mycobacteria","volume":"68","author":"Rezwan","year":"2007","journal-title":"J. Microbiol. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1016\/j.vaccine.2011.04.056","article-title":"Improved formulation and lyophilization cycle for rBCG vaccine","volume":"29","author":"Jin","year":"2011","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/jps.22458","article-title":"Trehalose: Current use and future applications","volume":"100","author":"Ohtake","year":"2011","journal-title":"J. Pharm. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/6\/270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:57:14Z","timestamp":1760187434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/6\/270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,10]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["pharmaceutics11060270"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11060270","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201904.0062.v1","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,10]]}}}