{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:56:45Z","timestamp":1787986605691,"version":"build-2784847793"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:00:00Z","timestamp":1570060800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"RANI Therapeutics, LLC"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biotherapeutic agents must be administered parenterally to obtain therapeutic blood concentrations, lowering patient compliance and complicating care. An oral delivery platform (ODP) was developed to deliver drugs into the small intestinal wall. This proof\u2010of\u2010concept study was performed in 17 anesthetized, laparotomized swine. In 8 swine weighing 17.4\u00a0\u00b1\u00a01.2\u00a0kg (mean\u00a0\u00b1\u00a0SEM), 20\u00a0IU of recombinant human insulin (RHI) were auto\u2010injected into the jejunal wall by placing the ODP inside the jejunum via an enterotomy. In 9 control swine weighing 17.0\u00a0\u00b1\u00a00.4\u00a0kg, 20\u00a0IU of RHI were injected subcutaneously. In both groups, under a 60\u201080\u00a0mg\/dL euglycemic glucose clamp, blood glucose was measured with a handheld glucometer and serum insulin was measured using ELISA, at 10\u2010minute intervals between \u221220 and +420\u00a0minutes after RHI delivery. The peak serum concentration of RHI was 517\u00a0\u00b1\u00a0109\u00a0pmol\/L in the ODP and 342\u00a0\u00b1\u00a050\u00a0pmol\/L in the subcutaneous group (ns). The areas under the insulin concentration curves (83\u00a0\u00b1\u00a018 and 81\u00a0\u00b1\u00a010\u00a0nmol\/L\u00b7min) were also similar in both groups. The mean time to peak serum concentration of insulin was 139\u00a0\u00b1\u00a042\u00a0minutes in the ODP and 227\u00a0\u00b1\u00a024\u00a0minutes in the subcutaneous group (ns). In conclusion, (a) The bioactivity of RHI was preserved after its delivery into the jejunal wall, (b) the intrajejunal route delivered insulin as rapidly and physiologically as the subcutaneous route, and (c) these pharmacokinetic and pharmacodynamic characteristics of RHI after intrajejunal delivery suggest that drugs currently administered parenterally, such as basal insulin, could be successfully delivered into the proximal intestinal wall via the ingestible capsule.<\/jats:p>","DOI":"10.1002\/prp2.522","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T13:59:46Z","timestamp":1570111186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Jejunal wall delivery of insulin via an ingestible capsule in anesthetized swine\u2014A pharmacokinetic and pharmacodynamic study"],"prefix":"10.1002","volume":"7","author":[{"given":"Mir","family":"Hashim","sequence":"first","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika","family":"Korupolu","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baber","family":"Syed","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Horlen","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC at InCube Laboratories San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simret","family":"Beraki","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Karamchedu","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvinder K.","family":"Dhalla","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-7424","authenticated-orcid":false,"given":"Rodolphe","family":"Ruffy","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir","family":"Imran","sequence":"additional","affiliation":[{"name":"Rani Therapeutics LLC San Jose California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.01.013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1348"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007990902905724"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2399"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181748"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2016.06.010"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.07.030"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12852"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.12.009"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.08.032"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.12.014"},{"key":"e_1_2_11_13_1","article-title":"Challenges for the oral delivery of macromolecules","volume":"289","author":"Goldberg M","year":"2003","journal-title":"Nat. Rev. Drug Discov"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1979.237.3.E214"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610050501"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","unstructured":"RuffyR HashimM DhallaAK et al.An Ingestible Capsule to Deliver Parenteral Pharmaceuticals into the Jejunal Wall. Abstract. 2019; American Diabetes Association Annual Meeting.https:\/\/ada.scientificposters.com\/epsAbstractADA.cfm?xml:id=1. Accessed August 19 2019.","DOI":"10.2337\/db19-125-LB"},{"key":"e_1_2_11_17_1","unstructured":"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03798912?term=ranipill&rank=1. Accessed August 19 2019."},{"key":"e_1_2_11_18_1","unstructured":"HashimM BerakiS KorupoluR et al.Pharmacokinetics of an Orally Delivered Antibody in Awake Dogs. Abstract presented at the 2019 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. Washington DC.2019."}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.522","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.522","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.522","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T12:40:50Z","timestamp":1694263250000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/prp2.522"],"URL":"https:\/\/doi.org\/10.1002\/prp2.522","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10]]},"assertion":[{"value":"2019-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00522"}}