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<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="20385183">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(10)00262-2"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=20385183&amp;db=pubmed&amp;nlmid=8607908"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="20385183"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/20385183/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=20385183&amp;db=pubmed&amp;nlmid=8607908"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="20385183"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/20385183/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/20385183/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="20385183" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F20385183%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="JIcPGxDVxEBWNT7YvciCX8kkRMpqE1Ej0vWUjn6h7foqHkdO8vVErgQYpQ7CxCcD"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
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Abstract
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<p>
There are many important considerations during preclinical development of cancer nanomedicines, including: 1) unique aspects of animal study design; 2) the difficulties in evaluating biological potency, especially for complex formulations; 3) the importance of analytical methods that can determine platform stability in vivo, and differentiate bound and free active pharmaceutical ingredient (API) in biological matrices; and 4) the appropriateness of current dose scaling techniques for estimation of clinical first-in-man dose from preclinical data. Biologics share many commonalities with nanotechnology products with regard to complexity and biological attributes, and can, in some cases, provide context for dealing with these preclinical issues. In other instances, such as the case of in vivo stability analysis, new approaches are required. This paper will discuss the significance of these preclinical issues, and present examples of current methods and best practices for addressing them. Where possible, these recommendations are justified using the existing regulatory guidance literature.
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Copyright 2010 Elsevier B.V. All rights reserved.
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Figures
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<p> Fig. 1 </p>
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<div class="figure-caption-contents"><p> Nanoplatform-drug stability. </p></div>
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<p> Fig. 1 </p>
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<div class="figure-caption-contents"><p> Nanoplatform-drug stability. </p></div>
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Fig. 1
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<div class="figure-caption-contents">Nanoplatform-drug stability.</div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><sup> 14 </sup> C-C6 ceramide and <sup> 3… </sup></div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><sup> 14 </sup> C-C6 ceramide and <sup> 3 </sup> H-DSPC plasma profiles. Reproduced with permission from Drug…</div>
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Fig. 2
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<div class="figure-caption-contents"><sup>14</sup>C-C6 ceramide and <sup>3</sup>H-DSPC plasma profiles. Reproduced with permission from Drug Metabolism and Disposition, Zolnik et al., 2008 [39]. Plasma time profiles are expressed as the percent injected dose per mL. (◆), <sup>3</sup>H-DSPC of ceramide liposome; (□), <sup>3</sup>H-DSPC of control liposome on y1 axis; (●) <sup>14</sup>C-ceramide on y2 axis. Each point represents the mean ± std. dev. from n=45 rats.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Blood concentration-time profiles for TNF-Au,… </p></div>
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<strong class="figure-label">
<p> Fig. 3 </p>
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<div class="figure-caption-contents"><p> Blood concentration-time profiles for TNF-Au, Au and native TNF. Blood profiles of colloidal… </p></div>
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Fig. 3
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<div class="figure-caption-contents">Blood concentration-time profiles for TNF-Au, Au and native TNF. Blood profiles of colloidal gold bound TNF (TNF-Au), gold (Au) and native TNF (Native TNF), are expressed as % injected dose/mL. The TNF concentration was determined by ELISA and gold concentration was determined by ICP-MS. Each symbol represents the mean±SD for that time point (<i>n</i>=45).</div>
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
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<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF/Au-hyperbolic stability model. The rectangular… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF/Au-hyperbolic stability model. The rectangular hyperbolic Michaelis-Menten type equation, ratio=1(1* <i> t </i> /( <i> t… </i> </p></div>
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Fig. 4
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<div class="figure-caption-contents">AuTNF/Au-hyperbolic stability model. The rectangular hyperbolic Michaelis-Menten type equation, ratio=1(1*<i>t</i>/(<i>t</i>+<i>t</i><sub>50</sub>)), was fit to the pooled AuTNF to gold (Au) concentration ratio-time profile. Data are presented as mean (<i>n</i>=4). Lines represent the fit of the hyperbolic stability model to the blood concentration-time data.</div>
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<strong class="figure-label">
<p> Fig. 5 </p>
</strong>
<div class="figure-caption-contents"><p> Pharmacokinetic model for TNF release.… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 5 </p>
</strong>
<div class="figure-caption-contents"><p> Pharmacokinetic model for TNF release. Pharmacokinetic parameters were obtained by fitting the blood… </p></div>
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Fig. 5
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<div class="figure-caption-contents">Pharmacokinetic model for TNF release. Pharmacokinetic parameters were obtained by fitting the blood concentration-time data for gold (<i>C</i><sub>Au</sub>) and AuTNF (<i>C</i><sub>T</sub>). The TNF release was estimated using the hyperbolic stability equation, <i>C</i><sub>Rel</sub>=<i>C</i><sub>T(0)</sub>*exp (<i>k</i><sub>1</sub>*<i>t</i>)*(<i>t</i>/(<i>t</i>+<i>t</i><sub>50</sub>). The first-order elimination constant (<i>k</i><sub>2</sub>) and concentration at time zero (<i>C</i><sub>N(0)</sub>) for native TNF (<i>C</i><sub>N</sub>) were fixed. The first-order elimination rate for gold (<i>k</i><sub>1</sub>), hyperbolic time to 50% TNF release (<i>t</i><sub>50</sub>), and time zero concentrations for gold (<i>C</i><sub>Au(0)</sub>) and AuTNF (<i>C</i><sub>T(0)</sub>) were obtained from fitting the kinetic model to the data.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Fig. 6 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF release model. The AuTNF… </p></div>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 6 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF release model. The AuTNF release model was fit to the pooled AuTNF… </p></div>
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<strong class="figure-label">
Fig. 6
</strong>
<div class="figure-caption-contents">AuTNF release model. The AuTNF release model was fit to the pooled AuTNF and gold(Au) blood concentration-time data, expressed as %ID/mL. Data are presented as mean (<i>n</i>=45). Lines represent the fit of the AuTNF release model to the blood concentration time data.</div>
</figcaption>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Fig. 7 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF release model simulations. The… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 7 </p>
</strong>
<div class="figure-caption-contents"><p> AuTNF release model simulations. The native TNF and released free TNF blood concentration… </p></div>
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<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 7
</strong>
<div class="figure-caption-contents">AuTNF release model simulations. The native TNF and released free TNF blood concentration data were simulated using the AuTNF release model and estimated pharmacokinetic parameters. Lines represent the simulated blood concentration-time data for the free TNF and native TNF comparison.</div>
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<strong class="figure-label">
<p> Fig. 8 </p>
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<div class="figure-caption-contents"><p> Hypothetical doseresponse. Preclinical dose-efficacy/dose-toxicity profiles… </p></div>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 8 </p>
</strong>
<div class="figure-caption-contents"><p> Hypothetical doseresponse. Preclinical dose-efficacy/dose-toxicity profiles for hypothetical drug X are displayed: MTD, maximum… </p></div>
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Fig. 8
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<div class="figure-caption-contents">Hypothetical doseresponse. Preclinical dose-efficacy/dose-toxicity profiles for hypothetical drug X are displayed: MTD, maximum tolerated dose ED50; effective dose 50=%; LD50, lethal dose 50%.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Fig. 9 </p>
</strong>
<div class="figure-caption-contents"><p> Allometric Scaling of AuTNF by… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 9 </p>
</strong>
<div class="figure-caption-contents"><p> Allometric Scaling of AuTNF by the Power Model. The clearance data for the… </p></div>
</div>
<figcaption id="figure-caption-8" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 9
</strong>
<div class="figure-caption-contents">Allometric Scaling of AuTNF by the Power Model. The clearance data for the CytImmune AuTNF formulation in multiple species were fit to the power equations CL=<i>a</i>*BW<sup><i>b</i></sup>. Data points are presented as the mean (<i>n</i>=2) of two clinical and rabbit dose levels, and the single estimate from a single rat dose level. Lines represent the fit of the model to the preclinical data, excluding the clinical data.</div>
</figcaption>
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c80/2921639/4d2c3f1afd1e/nihms-195748-f0010.gif"
alt="Fig. 10" />
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<strong class="figure-label">
<p> Fig. 10 </p>
</strong>
<div class="figure-caption-contents"><p> Allometric scaling of AuTNF by… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 10 </p>
</strong>
<div class="figure-caption-contents"><p> Allometric scaling of AuTNF by the brain weight (BrW) product model. The clearance… </p></div>
</div>
<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 10
</strong>
<div class="figure-caption-contents">Allometric scaling of AuTNF by the brain weight (BrW) product model. The clearance data were fit to the power equations BrW×CL=<i>a</i>*BW<sup><i>b</i></sup>. Data points are presented as the mean (<i>n</i>=2) for both human and rabbit dose levels, and the single estimate for rat. Lines represent the fit of the model to all data.</div>
</figcaption>
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