Sterilization of Silver Nanoparticles Using Standard Gamma Irradiation Procedure Affects Particle Integrity and Biocompatibility
Identifieur interne : 004691 ( Pmc/Curation ); précédent : 004690; suivant : 004692Sterilization of Silver Nanoparticles Using Standard Gamma Irradiation Procedure Affects Particle Integrity and Biocompatibility
Auteurs : Jiwen Zheng ; Jeffrey D. Clogston ; Anil K. Patri ; Marina A. Dobrovolskaia ; Scott E. McneilSource :
- Journal of nanomedicine & nanotechnology [ 2157-7439 ] ; 2011.
Abstract
Silver nanoparticles are commonly used in a variety of commercial and medical products. Here we investigate the effects of standard sterilization methods, including heat/steam (autoclave) and gamma-irradiation on the structural integrity and biocompatibility of citrate-stabilized silver nanoparticles with nominal sizes of 20, 40, 60 and 80 nm. Particle size, shape and in vitro biocompatibility were studied pre- and post-sterilization. Sterilization by gamma irradiation at dose levels commonly used in medical device industry (15, 25 and 50 kGy) resulted in dramatic changes in particle size and morphology, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Exposing the particles to a chemical producer of hydroxyl radicals (N-hydroxy-2-pyridinethione) allowed us to duplicate the sterilization-based changes in size and morphology, implying a free radical mechanism of action. Compared to untreated controls, we also observed a three- to five-fold increase in tendency of sterilized silver nanoparticles to cause platelet aggregation, a sensitive in vitro indicator of thrombogenicity.
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DOI: 10.4172/2157-7439.S5-001
PubMed: 25035814
PubMed Central: 4098784
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<author><name sortKey="Zheng, Jiwen" sort="Zheng, Jiwen" uniqKey="Zheng J" first="Jiwen" last="Zheng">Jiwen Zheng</name>
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<author><name sortKey="Clogston, Jeffrey D" sort="Clogston, Jeffrey D" uniqKey="Clogston J" first="Jeffrey D." last="Clogston">Jeffrey D. Clogston</name>
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<author><name sortKey="Patri, Anil K" sort="Patri, Anil K" uniqKey="Patri A" first="Anil K." last="Patri">Anil K. Patri</name>
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<author><name sortKey="Dobrovolskaia, Marina A" sort="Dobrovolskaia, Marina A" uniqKey="Dobrovolskaia M" first="Marina A." last="Dobrovolskaia">Marina A. Dobrovolskaia</name>
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<front><div type="abstract" xml:lang="en"><p id="P1">Silver nanoparticles are commonly used in a variety of commercial and medical products. Here we investigate the effects of standard sterilization methods, including heat/steam (autoclave) and gamma-irradiation on the structural integrity and biocompatibility of citrate-stabilized silver nanoparticles with nominal sizes of 20, 40, 60 and 80 nm. Particle size, shape and in vitro biocompatibility were studied pre- and post-sterilization. Sterilization by gamma irradiation at dose levels commonly used in medical device industry (15, 25 and 50 kGy) resulted in dramatic changes in particle size and morphology, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Exposing the particles to a chemical producer of hydroxyl radicals (N-hydroxy-2-pyridinethione) allowed us to duplicate the sterilization-based changes in size and morphology, implying a free radical mechanism of action. Compared to untreated controls, we also observed a three- to five-fold increase in tendency of sterilized silver nanoparticles to cause platelet aggregation, a sensitive in vitro indicator of thrombogenicity.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101562615</journal-id>
<journal-id journal-id-type="pubmed-jr-id">39267</journal-id>
<journal-id journal-id-type="nlm-ta">J Nanomed Nanotechnol</journal-id>
<journal-id journal-id-type="iso-abbrev">J Nanomed Nanotechnol</journal-id>
<journal-title-group><journal-title>Journal of nanomedicine & nanotechnology</journal-title>
</journal-title-group>
<issn pub-type="epub">2157-7439</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25035814</article-id>
<article-id pub-id-type="pmc">4098784</article-id>
<article-id pub-id-type="doi">10.4172/2157-7439.S5-001</article-id>
<article-id pub-id-type="manuscript">NIHMS438765</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Sterilization of Silver Nanoparticles Using Standard Gamma Irradiation Procedure Affects Particle Integrity and Biocompatibility</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zheng</surname>
<given-names>Jiwen</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Clogston</surname>
<given-names>Jeffrey D.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Patri</surname>
<given-names>Anil K.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Dobrovolskaia</surname>
<given-names>Marina A.</given-names>
</name>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McNeil</surname>
<given-names>Scott E.</given-names>
</name>
</contrib>
<aff id="A1">Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD21702</aff>
</contrib-group>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding author: Marina A. Dobrovolskaia, Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD21702, Tel: 301-360-3542; Fax: 301-846-6399; <email>marina@mail.nih.gov</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>1</day>
<month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>25</day>
<month>10</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><day>25</day>
<month>10</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>7</month>
<year>2014</year>
</pub-date>
<volume>2011</volume>
<issue>Suppl 5</issue>
<fpage>001</fpage>
<lpage></lpage>
<pmc-comment>elocation-id from pubmed: 10.4172/2157-7439.S5-001</pmc-comment>
<permissions><copyright-statement>Copyright: © 2012 Zheng J, et al.</copyright-statement>
<copyright-year>2012</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://omicsonline.org/ArchiveJNMNT/SpecialissuesJNMNT-S5.php"></self-uri>
<abstract><p id="P1">Silver nanoparticles are commonly used in a variety of commercial and medical products. Here we investigate the effects of standard sterilization methods, including heat/steam (autoclave) and gamma-irradiation on the structural integrity and biocompatibility of citrate-stabilized silver nanoparticles with nominal sizes of 20, 40, 60 and 80 nm. Particle size, shape and in vitro biocompatibility were studied pre- and post-sterilization. Sterilization by gamma irradiation at dose levels commonly used in medical device industry (15, 25 and 50 kGy) resulted in dramatic changes in particle size and morphology, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Exposing the particles to a chemical producer of hydroxyl radicals (N-hydroxy-2-pyridinethione) allowed us to duplicate the sterilization-based changes in size and morphology, implying a free radical mechanism of action. Compared to untreated controls, we also observed a three- to five-fold increase in tendency of sterilized silver nanoparticles to cause platelet aggregation, a sensitive in vitro indicator of thrombogenicity.</p>
</abstract>
<kwd-group><kwd>Silver nanoparticles</kwd>
<kwd>Gamma irradiation</kwd>
<kwd>Autoclave</kwd>
<kwd>Sterilization</kwd>
<kwd>Particle size</kwd>
<kwd>Hematocompatibility</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Hydrodynamic size of silver nanoparticles with nominal size 20 nm (A), 40 nm (B), 60 nm(C), and 80 nm (D) before and after gamma-irradiation</p>
</caption>
<graphic xlink:href="nihms438765f1"></graphic>
</fig>
<fig id="F2" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Representative TEM images of silver nanoparticles (20, 40, 60, and 80 nm) before and after sterilization treatments. The sterilization included autoclave and gamma irradiation at 3 different doses (15, 25 and 50kGy). Shown are results from irradiation at 50kGy, other doses resulted in similar changes. All scale bars are 100 nm unless otherwise noted.</p>
</caption>
<graphic xlink:href="nihms438765f2"></graphic>
</fig>
<fig id="F3" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Representative TEM images of 20 nm, 40 nm, 60 nm, and 80 nm silver nanoparticles on silicon Smart TEM grids, before and after gamma irradiation at 50 kGy. TEM data clearly show gamma irradiation induced degradation of the silver colloids, resulting in both small particles and large aggregates.</p>
</caption>
<graphic xlink:href="nihms438765f3"></graphic>
</fig>
<fig id="F4" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>Analysis of silver nanoparticles in platelet aggregation test. Silver nanoparticles with nominal size of 20 nm (A), 40 nm (B), 60 nm (C) and 80 nm (D), untreated or sterilized with various methods, were evaluated for their potential effects on the cellular component of the blood coagulation cascade. For each nanoparticle formulation, three independent samples were prepared and analyzed in duplicate (%CV < 20). Each bar represents the mean response of these three independent samples plus SD.</p>
</caption>
<graphic xlink:href="nihms438765f4"></graphic>
</fig>
<fig id="F5" orientation="portrait" position="float"><label>Figure 5</label>
<caption><p>Hypothetical mechanism for morphology change upon exposure to gamma irradiation and EtOx. Hydroxyl radicals produced during gamma irradiation oxidize the silver nanoparticles to Ag+ ions then reducing agents in solution competitively reduce Ag+ ions to Ag atoms. Since there is not sufficient fresh stabilizer in the solution, coalescence is not well controlled, causing the formed particles to display irregular shapes (e.g. the small particles, “ribbon”, “sheet” and “wire” structures we observed).</p>
</caption>
<graphic xlink:href="nihms438765f5"></graphic>
</fig>
<fig id="F6" orientation="portrait" position="float"><label>Figure 6</label>
<caption><p>(A) UV-vis spectra of 20 nm silver nanoparticles with treatment of HPT (5 μM), alone or in combination with UV treatment. Addition of UV treatment shows dramatic absorbance differences. (B) TEM images of 20 nm citrate-stabilized silver nanoparticles: untreated (control), treated with UV for 3 hours, treated with HPT (5 μM) for 3 hours, and treated with HPT (5 μM) and UV for 3 hours. From the inserts, it is clear the crystal structure of the silver was destroyed by UV, HPT and HPT + UV treatments.</p>
</caption>
<graphic xlink:href="nihms438765f6"></graphic>
</fig>
<table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label>
<caption><p>Summary of size analysis of silver nanoparticles before and after sterilization treatments by autoclave and various doses of gamma irradiation.</p>
</caption>
<table frame="box" rules="cols"><thead><tr><th align="left" rowspan="1" colspan="1">Sample</th>
<th align="left" rowspan="1" colspan="1">Nominal Size (nm)</th>
<th align="left" rowspan="1" colspan="1">DLS, Z-Avg (nm)</th>
<th align="left" rowspan="1" colspan="1">TEM (nm)</th>
</tr>
<tr><th align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</th>
</tr>
</thead>
<tbody><tr><td align="left" colspan="4" valign="bottom" rowspan="1">20 nm silver nanoparticles
<hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">untreated</td>
<td align="left" rowspan="1" colspan="1">20</td>
<td align="left" rowspan="1" colspan="1">34.0 ± 0.4</td>
<td align="left" rowspan="1" colspan="1">36.4 ± 5.1</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">autoclaved</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">33.4 ± 0.2</td>
<td align="left" rowspan="1" colspan="1">37.2 ± 5.7</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 15kGy</td>
<td align="left" rowspan="3" valign="middle" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 25kGy</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 50kGy</td>
<td align="left" rowspan="1" colspan="1">polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1">40 nm silver nanoparticles
<hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">untreated</td>
<td align="left" rowspan="1" colspan="1">40</td>
<td align="left" rowspan="1" colspan="1">38.3 ± 0.5</td>
<td align="left" rowspan="1" colspan="1">55.9 ± 9.6</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">autoclaved</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">37.8 ± 0.2</td>
<td align="left" rowspan="1" colspan="1">54.9 ± 8.4</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 15kGy</td>
<td align="left" rowspan="3" valign="middle" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 25kGy</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 50kGy</td>
<td align="left" rowspan="1" colspan="1">polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1">60 nm silver nanoparticles
<hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">untreated</td>
<td align="left" rowspan="1" colspan="1">60</td>
<td align="left" rowspan="1" colspan="1">65.3 ± 0.4</td>
<td align="left" rowspan="1" colspan="1">78.3 ± 12.3</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">autoclaved</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">67.5 ± 1.0</td>
<td align="left" rowspan="1" colspan="1">74.6 ± 10.5</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 15kGy</td>
<td align="left" rowspan="3" valign="middle" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 25kGy</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 50kGy</td>
<td align="left" rowspan="1" colspan="1">polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1">80 nm silver nanoparticles
<hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">untreated</td>
<td align="left" rowspan="1" colspan="1">80</td>
<td align="left" rowspan="1" colspan="1">90.7 ± 0.3</td>
<td align="left" rowspan="1" colspan="1">107.2 ± 14.1</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">autoclaved</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">90.0 ± 0.6</td>
<td align="left" rowspan="1" colspan="1">109.3 ± 13.2</td>
</tr>
<tr><td align="left" colspan="4" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 15kGy</td>
<td align="left" rowspan="3" valign="middle" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 25kGy</td>
<td align="left" rowspan="1" colspan="1">Polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">γ- irradiated 50kGy</td>
<td align="left" rowspan="1" colspan="1">polydispersed</td>
<td align="left" rowspan="1" colspan="1">irregular shape</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="TFN1"><p>Note: numbers after the ± symbol represent standard deviations. For the DLS measurements, these values indicate the reproducibility of the measurement (n ≥ 12), not the polydispersity of the size distribution</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>
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