The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy
Abstract Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assemb...
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| Veröffentlicht in: | Biomaterials 2011-06, Vol.32 (16), p.4000-4008 |
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| creator | Fung, Shan-Yu Oyaizu, Takeshi Yang, Hong Yuan, Yongfang Han, Bing Keshavjee, Shaf Liu, Mingyao |
| description | Abstract Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. The promising therapeutic efficacy and the formulation strategy developed in this work may help further translate PP2 and other hydrophobic therapeutic agents into clinical applications. |
| doi_str_mv | 10.1016/j.biomaterials.2011.02.005 |
| format | Article |
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For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. The promising therapeutic efficacy and the formulation strategy developed in this work may help further translate PP2 and other hydrophobic therapeutic agents into clinical applications.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2011.02.005</identifier><identifier>PMID: 21376387</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Acute inflammatory response ; Acute Lung Injury - chemically induced ; Acute Lung Injury - drug therapy ; Advanced Basic Science ; Amino Acids - chemistry ; Amino Acids - therapeutic use ; Animals ; Biocompatibility ; Blotting, Western ; Cell Line ; Dentistry ; Drug delivery ; Hemolysis - drug effects ; Humans ; Lipopolysaccharides - toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Nanoformulation ; NIH 3T3 Cells ; Oligopeptides - therapeutic use ; Pyrimidines - chemistry ; Pyrimidines - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Self-assembling peptide</subject><ispartof>Biomaterials, 2011-06, Vol.32 (16), p.4000-4008</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-1dd31dfa90e2375b7ef98f87ade1aa7d9cbf0100c3d9ab5e4eecf2427937b3a23</citedby><cites>FETCH-LOGICAL-c532t-1dd31dfa90e2375b7ef98f87ade1aa7d9cbf0100c3d9ab5e4eecf2427937b3a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2011.02.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21376387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fung, Shan-Yu</creatorcontrib><creatorcontrib>Oyaizu, Takeshi</creatorcontrib><creatorcontrib>Yang, Hong</creatorcontrib><creatorcontrib>Yuan, Yongfang</creatorcontrib><creatorcontrib>Han, Bing</creatorcontrib><creatorcontrib>Keshavjee, Shaf</creatorcontrib><creatorcontrib>Liu, Mingyao</creatorcontrib><title>The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. The promising therapeutic efficacy and the formulation strategy developed in this work may help further translate PP2 and other hydrophobic therapeutic agents into clinical applications.</description><subject>Acute inflammatory response</subject><subject>Acute Lung Injury - chemically induced</subject><subject>Acute Lung Injury - drug therapy</subject><subject>Advanced Basic Science</subject><subject>Amino Acids - chemistry</subject><subject>Amino Acids - therapeutic use</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Dentistry</subject><subject>Drug delivery</subject><subject>Hemolysis - drug effects</subject><subject>Humans</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanoformulation</subject><subject>NIH 3T3 Cells</subject><subject>Oligopeptides - therapeutic use</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - therapeutic use</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Self-assembling peptide</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1TAQhS0EopfCKyCLDasE_yQ3CQskVH6lSixa1pZjT-ikiR1sp1IehPfF4RaEWLGyrTnnjMbfEPKCs5Izfnw1lj36WScIqKdYCsZ5yUTJWP2AHHjbtEXdsfohOTBeiaI7cnFGnsQ4svxmlXhMzgSXzVG2zYH8uL4BuvgELuUw6gfqtPPR6Amo8XOPTif0Lu6VCNNQ6Bhh7id03-gCS0ILkWpnqZ7ReaoN2l_alGOvgqFpCz6iA3qbkyJQdDfYY_Ih37J6TUCnNWehG9ew7bagl-0peTTk0eDZ_XlOvn54f33xqbj88vHzxdvLwtRSpIJbK7kddMdAyKbuGxi6dmgbbYFr3djO9APjjBlpO93XUAGYQVSi6WTTSy3kOXl5yl2C_75CTGrGaGCatAO_RtUeu1Z2smqz8vVJafI8McCgloCzDpviTO1U1Kj-pqJ2KooJlalk8_P7Nms_g_1j_Y0hC96dBJCHvUMIKhoEZ8BiAJOU9fh_fd78E2MyKMwwb2GDOPo1uN3DVcwGdbXvx74ePP8RFy2XPwF8_b5X</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Fung, Shan-Yu</creator><creator>Oyaizu, Takeshi</creator><creator>Yang, Hong</creator><creator>Yuan, Yongfang</creator><creator>Han, Bing</creator><creator>Keshavjee, Shaf</creator><creator>Liu, Mingyao</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110601</creationdate><title>The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy</title><author>Fung, Shan-Yu ; Oyaizu, Takeshi ; Yang, Hong ; Yuan, Yongfang ; Han, Bing ; Keshavjee, Shaf ; Liu, Mingyao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-1dd31dfa90e2375b7ef98f87ade1aa7d9cbf0100c3d9ab5e4eecf2427937b3a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acute inflammatory response</topic><topic>Acute Lung Injury - chemically induced</topic><topic>Acute Lung Injury - drug therapy</topic><topic>Advanced Basic Science</topic><topic>Amino Acids - chemistry</topic><topic>Amino Acids - therapeutic use</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Dentistry</topic><topic>Drug delivery</topic><topic>Hemolysis - drug effects</topic><topic>Humans</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nanoformulation</topic><topic>NIH 3T3 Cells</topic><topic>Oligopeptides - therapeutic use</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - therapeutic use</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Self-assembling peptide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fung, Shan-Yu</creatorcontrib><creatorcontrib>Oyaizu, Takeshi</creatorcontrib><creatorcontrib>Yang, Hong</creatorcontrib><creatorcontrib>Yuan, Yongfang</creatorcontrib><creatorcontrib>Han, Bing</creatorcontrib><creatorcontrib>Keshavjee, Shaf</creatorcontrib><creatorcontrib>Liu, Mingyao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fung, Shan-Yu</au><au>Oyaizu, Takeshi</au><au>Yang, Hong</au><au>Yuan, Yongfang</au><au>Han, Bing</au><au>Keshavjee, Shaf</au><au>Liu, Mingyao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>32</volume><issue>16</issue><spage>4000</spage><epage>4008</epage><pages>4000-4008</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. 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| subjects | Acute inflammatory response Acute Lung Injury - chemically induced Acute Lung Injury - drug therapy Advanced Basic Science Amino Acids - chemistry Amino Acids - therapeutic use Animals Biocompatibility Blotting, Western Cell Line Dentistry Drug delivery Hemolysis - drug effects Humans Lipopolysaccharides - toxicity Male Mice Mice, Inbred BALB C Nanoformulation NIH 3T3 Cells Oligopeptides - therapeutic use Pyrimidines - chemistry Pyrimidines - therapeutic use Rats Rats, Sprague-Dawley Self-assembling peptide |
| title | The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy |
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