{"id":248,"date":"2020-07-13T10:26:01","date_gmt":"2020-07-13T09:26:01","guid":{"rendered":"http:\/\/makitbe.com\/?p=248"},"modified":"2020-11-30T16:51:05","modified_gmt":"2020-11-30T15:51:05","slug":"a-luminal-unfolding-microneedle-injector-for-oral-delivery-of-macromolecules-nature-medicine","status":"publish","type":"post","link":"https:\/\/makitbe.com\/index.php\/2020\/07\/13\/a-luminal-unfolding-microneedle-injector-for-oral-delivery-of-macromolecules-nature-medicine\/","title":{"rendered":"A luminal unfolding microneedle injector for oral delivery of macromolecules &#8211; Nature Medicine"},"content":{"rendered":"<p>&#8220;A luminal unfolding microneedle injector for oral delivery of macromolecules&#8221;<\/p>\n<section lang=\"en\" aria-labelledby=\"Abs1\">\n<div id=\"Abs1-section\" class=\"c-article-section\">\n<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Abstract<\/h2>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes<sup><a id=\"ref-link-section-d33798e857\" title=\"Turner, R. C., Cull, C. A., Frighi, V. &amp; Holman, R. R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). J. Am. Med. Assoc. 281, 2005\u20132012 (1999).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d33798e860\" title=\"Pratley, R. E. et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 375, 1447\u20131456 (2010).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications<sup><a id=\"ref-link-section-d33798e864\" title=\"Korytkowski, M. When oral agents fail: practical barriers to starting insulin. Int. J. Obes. 26, S18\u2013S24 (2002).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9?fbclid=IwAR3SOhYka1bPkN6iyvlXdIO0qQV8CTkxNYONr584q2YThPKoni7aRPwz7s8#ref-CR3\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">3<\/a>,<a id=\"ref-link-section-d33798e864_1\" title=\"Boye, K. S. et al. Utilities and disutilities for attributes of injectable treatments for type 2 diabetes. Eur. J. Heal. Econ. 12, 219\u2013230 (2011).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9?fbclid=IwAR3SOhYka1bPkN6iyvlXdIO0qQV8CTkxNYONr584q2YThPKoni7aRPwz7s8#ref-CR4\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">4<\/a>,<a id=\"ref-link-section-d33798e867\" title=\"Calvert, M. J., McManus, R. J. &amp; Freemantle, N. Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study. Br. J. Gen. Pract. 57, 455\u2013460 (2007).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR5\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\">5<\/a><\/sup>. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort<sup><a id=\"ref-link-section-d33798e871\" title=\"Boye, K. S. et al. Utilities and disutilities for attributes of injectable treatments for type 2 diabetes. Eur. J. Heal. Econ. 12, 219\u2013230 (2011).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR4\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\">4<\/a><\/sup>, show greater chemical stability at high temperatures<sup><a id=\"ref-link-section-d33798e875\" title=\"Cleland, J. &amp; Langer, R. in Formulation and Delivery of Proteins and Peptides (eds. Cleland, J. L. &amp; Langer, R.) 1\u201319 (American Chemical Society, 1994).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR6\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 6\">6<\/a><\/sup>, and do not generate biohazardous needle waste<sup><a id=\"ref-link-section-d33798e879\" title=\"Dallel, N., Kacem, M., Nabouli, R. M. &amp; El May, M. Disposal of insulin syringes by diabetic patients. Report of 100 patients.Tunis. Med. 83, 390\u2013392 (2005).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup>. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract<sup><a id=\"ref-link-section-d33798e884\" title=\"Anselmo, A. C., Gokarn, Y. &amp; Mitragotri, S. Non-invasive delivery strategies for biologics. Nat. Rev. Drug Discov. 18, 19\u201340 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-019-0598-9#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\">8<\/a><\/sup>. We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake &gt;10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<p><img loading=\"lazy\" class=\"alignnone size-full wp-image-244\" src=\"http:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00071.jpg\" alt=\"\" width=\"1920\" height=\"1080\" srcset=\"https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00071.jpg 1920w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00071-300x169.jpg 300w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00071-768x432.jpg 768w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00071-1024x576.jpg 1024w\" sizes=\"(max-width: 767px) 89vw, (max-width: 1000px) 54vw, (max-width: 1071px) 543px, 580px\" \/><br \/>\n<img loading=\"lazy\" class=\"alignnone size-full wp-image-245\" src=\"http:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00246.jpg\" alt=\"\" width=\"1920\" height=\"1080\" srcset=\"https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00246.jpg 1920w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00246-300x169.jpg 300w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00246-768x432.jpg 768w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00246-1024x576.jpg 1024w\" sizes=\"(max-width: 767px) 89vw, (max-width: 1000px) 54vw, (max-width: 1071px) 543px, 580px\" \/><br \/>\n<img loading=\"lazy\" class=\"alignnone size-full wp-image-246\" src=\"http:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00374.jpg\" alt=\"\" width=\"1920\" height=\"1080\" srcset=\"https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00374.jpg 1920w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00374-300x169.jpg 300w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00374-768x432.jpg 768w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00374-1024x576.jpg 1024w\" sizes=\"(max-width: 767px) 89vw, (max-width: 1000px) 54vw, (max-width: 1071px) 543px, 580px\" \/><\/p>\n<p><img loading=\"lazy\" class=\"alignnone size-full wp-image-247\" src=\"http:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00643.jpg\" alt=\"\" width=\"1920\" height=\"1080\" srcset=\"https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00643.jpg 1920w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00643-300x169.jpg 300w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00643-768x432.jpg 768w, https:\/\/makitbe.com\/wp-content\/uploads\/2020\/07\/PROJET-LUMI-00643-1024x576.jpg 1024w\" sizes=\"(max-width: 767px) 89vw, (max-width: 1000px) 54vw, (max-width: 1071px) 543px, 580px\" \/><br \/>\nhttps:\/\/www.nature.com\/articles\/s41591-019-0598-9?fbclid=IwAR3SOhYka1bPkN6iyvlXdIO0qQV8CTkxNYONr584q2YThPKoni7aRPwz7s8<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;A luminal unfolding microneedle injector for oral delivery of macromolecules&#8221; Abstract Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications3,4,5. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort4, show greater &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/makitbe.com\/index.php\/2020\/07\/13\/a-luminal-unfolding-microneedle-injector-for-oral-delivery-of-macromolecules-nature-medicine\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;A luminal unfolding microneedle injector for oral delivery of macromolecules &#8211; Nature Medicine&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":245,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/posts\/248"}],"collection":[{"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/comments?post=248"}],"version-history":[{"count":2,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/posts\/248\/revisions"}],"predecessor-version":[{"id":362,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/posts\/248\/revisions\/362"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/media\/245"}],"wp:attachment":[{"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/media?parent=248"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/categories?post=248"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/makitbe.com\/index.php\/wp-json\/wp\/v2\/tags?post=248"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}