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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ETeriparatide is absorbed across the nasal mucosa in two animal models, paving the way for a Phase 1 clinical trial to begin in late 2013. This article presents preclinical data of nanoenabled intranasal teriparatide for the treatment of osteoporosis.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHormone Therapy\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHormone Therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETeriparatide is absorbed across the nasal mucosa in two animal models, paving the way for a Phase 1 clinical trial to begin in late 2013. Faron Jordan, PhD, Critical Pharmaceuticals, Nottingham, United Kingdom, presented preclinical data of nanoenabled intranasal teriparatide for the treatment of osteoporosis.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAdministration of parathyroid hormone (PTH) is effective in promoting bone formation, resulting in increased bone mineral density, in patients with osteoporosis [Hodsman AB et al. \u003Cem\u003EEndocr Rev\u003C\/em\u003E 2005]. Teriparatide is a peptide containing recombinant human PTH and is currently administered by daily injection. Intranasal delivery of teriparatide would be an attractive alternative to daily injections; however, peptide absorption across the nasal mucosa is limited [Illum L et al. \u003Cem\u003EJ Control Release\u003C\/em\u003E 2012]. The purpose of this preclinical study is to demonstrate that the CriticalSorb\u2122 nasal delivery system developed by Critical Pharmaceuticals promotes the absorption of teriparatide and to establish the bioavailability of lead formulations prior to the initiation of a Phase 1 clinical trial.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the preclinical study, 80 \u03bcg\/kg of the teriparatide formulations were administered intranasally, using a narrow tipped pipette, to 4 conscious Sprague Dawley rats. Conscious New Zealand white female rabbits received 67 \u03bcg\/kg of the lead teriparatide formulations. In both populations, subsequent subcutaneous injections were administered to allow relative bioavailability measurements. Following drug administration, blood was drawn for up to 6 hours and analyzed by liquid chromatography mass spectrometry\/mass spectrometry. The bioactivity of the teriparatide CriticalSorb formulations were evaluated in a human osteoblast-like Saos-2 cell culture system.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe bioavailability of the teriparatide\/CriticalSorb formulation was 79% of subcutaneous teriparatide injection in rats (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Intranasal administration of teriparatide without CriticalSorb resulted in very low levels of absorption. In rabbits, the lead formulation of teriparatide and CriticalSorb resulted in a bioavailability of 64% of the subcutaneous injection of teriparatide.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the \u003Cem\u003Ein vitro\u003C\/em\u003E assay system, the cyclic adenosine monophosphate (cAMP) response to the teriparatide\/CriticalSorb formulations was 113% greater than that of PTH 10 nm alone and PTH 10 nm in formulation with sodium hyaluronate, poloxamer 407, or chitosan (p\u0026lt;0.05). CriticalSorb without teriparatide did not elicit a cAMP response.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/10\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Bioavailability of Intranasal Teriparatide\/CriticalSorb Formulations in Animal Models\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1348737956\u0022 data-figure-caption=\u0022Bioavailability of Intranasal Teriparatide\/CriticalSorb Formulations in Animal Models\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/10\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/10\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/10\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13308\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EBioavailability of Intranasal Teriparatide\/CriticalSorb Formulations in Animal Models\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EIN=intranasal; SC=subcutaneous.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from F Jordan, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EIn the preclinical study, the stability of teriparatide was optimal with the addition of 5% w\/v mannitol and 3% w\/v of methionine at 37\u00b0C. The stability of teriparatide in this solution has remained stable at 12 weeks and long-term testing is currently underway.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe anticipated Phase 1 trial will have a 5-way crossover design to evaluate the safety of the teriparatide\/CriticalSorb lead formulation compared with subcutaneous injection of teriparatide in postmenopausal healthy women. The primary endpoint of the Phase 1 trial will be to establish the pharmacokinetics of teriparatide following intranasal delivery. Currently, three doses of the teriparatide\/CriticalSorb formulation are planned.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDr. Jordan stated that the data from the preclinical study suggest that the intranasal delivery of teriparatide is absorbed across the nasal mucosa in two animal models. The Phase 1 trial is expected to begin at the end of 2013, with results expected in early 2014.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/10\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzno8e\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzno8e\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}