Thymopentin Nanoparticles Engineered with High Loading Efficiency, Improved Pharmacokinetic Properties, and Enhanced Immunostimulating Effect Using Soybean Phospholipid and PHBHHx Polymer
Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). T...
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| Veröffentlicht in: | Molecular pharmaceutics 2014-10, Vol.11 (10), p.3371-3377 |
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| creator | Wu, Chengyu Zhang, Mengtian Zhang, Zhirong Wan, Ka-Wai Ahmed, Waqar Phoenix, David A Elhissi, Abdelbary M. A Sun, Xun |
| description | Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, −32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5. |
| doi_str_mv | 10.1021/mp400722r |
| format | Article |
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A ; Sun, Xun</creator><creatorcontrib>Wu, Chengyu ; Zhang, Mengtian ; Zhang, Zhirong ; Wan, Ka-Wai ; Ahmed, Waqar ; Phoenix, David A ; Elhissi, Abdelbary M. A ; Sun, Xun</creatorcontrib><description>Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, −32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5.</description><identifier>ISSN: 1543-8384</identifier><identifier>EISSN: 1543-8392</identifier><identifier>DOI: 10.1021/mp400722r</identifier><identifier>PMID: 24641274</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Adjuvants, Immunologic - chemistry ; Animals ; Glycine max - chemistry ; Male ; Nanoparticles - chemistry ; Phospholipids - chemistry ; Polymers - chemistry ; Rats ; Rats, Wistar ; Thymopentin - chemistry ; Thymopentin - immunology</subject><ispartof>Molecular pharmaceutics, 2014-10, Vol.11 (10), p.3371-3377</ispartof><rights>Copyright © 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-6257b3e54c05dc4d2618c7d55738e518ad49744420dd031651be54419b264cc73</citedby><cites>FETCH-LOGICAL-a315t-6257b3e54c05dc4d2618c7d55738e518ad49744420dd031651be54419b264cc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/mp400722r$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/mp400722r$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24641274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Chengyu</creatorcontrib><creatorcontrib>Zhang, Mengtian</creatorcontrib><creatorcontrib>Zhang, Zhirong</creatorcontrib><creatorcontrib>Wan, Ka-Wai</creatorcontrib><creatorcontrib>Ahmed, Waqar</creatorcontrib><creatorcontrib>Phoenix, David A</creatorcontrib><creatorcontrib>Elhissi, Abdelbary M. A</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><title>Thymopentin Nanoparticles Engineered with High Loading Efficiency, Improved Pharmacokinetic Properties, and Enhanced Immunostimulating Effect Using Soybean Phospholipid and PHBHHx Polymer</title><title>Molecular pharmaceutics</title><addtitle>Mol. Pharmaceutics</addtitle><description>Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, −32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5.</description><subject>Adjuvants, Immunologic - chemistry</subject><subject>Animals</subject><subject>Glycine max - chemistry</subject><subject>Male</subject><subject>Nanoparticles - chemistry</subject><subject>Phospholipids - chemistry</subject><subject>Polymers - chemistry</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Thymopentin - chemistry</subject><subject>Thymopentin - immunology</subject><issn>1543-8384</issn><issn>1543-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0c9OwyAcwHFiNP6ZHnwBw8WDiVOg0HZHXaZdsugS9dxQYCtaoIFO7bP5cqKbO3kCki-fEH4AnGJ0hRHB16alCGWE-B1wiBlNhnkyIrvbfU4PwFEIrwgRykiyDw4ITSkmGT0EX891b1yrbKctfODWtdx3WjQqwIldaquUVxJ-6K6GhV7WcOa41HYJJ4uFFlpZ0V_CqWm9e4_ZvObecOHe4r2IwLmPcuRUuITcyijW3IoYTo1ZWRc6bVYN7zaeEh18CT-HJ9dXitvoudDWrtGtlr_AvLgtik84d01vlD8GewveBHWyWQfg5W7yPC6Gs8f76fhmNuQJZt0wJSyrEsWoQEwKKkmKc5FJxrIkVwznXNJRRiklSEqU4JThKsYUjyqSUiGyZAAu1q7wLgSvFmXrteG-LzEqfwZQbgcQ27N1264qo-S2_PvxGJyvAy5C-epW3san_wN9AxgKkDU</recordid><startdate>20141006</startdate><enddate>20141006</enddate><creator>Wu, Chengyu</creator><creator>Zhang, Mengtian</creator><creator>Zhang, Zhirong</creator><creator>Wan, Ka-Wai</creator><creator>Ahmed, Waqar</creator><creator>Phoenix, David A</creator><creator>Elhissi, Abdelbary M. A</creator><creator>Sun, Xun</creator><general>American Chemical Society</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></search><sort><creationdate>20141006</creationdate><title>Thymopentin Nanoparticles Engineered with High Loading Efficiency, Improved Pharmacokinetic Properties, and Enhanced Immunostimulating Effect Using Soybean Phospholipid and PHBHHx Polymer</title><author>Wu, Chengyu ; Zhang, Mengtian ; Zhang, Zhirong ; Wan, Ka-Wai ; Ahmed, Waqar ; Phoenix, David A ; Elhissi, Abdelbary M. A ; Sun, Xun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-6257b3e54c05dc4d2618c7d55738e518ad49744420dd031651be54419b264cc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adjuvants, Immunologic - chemistry</topic><topic>Animals</topic><topic>Glycine max - chemistry</topic><topic>Male</topic><topic>Nanoparticles - chemistry</topic><topic>Phospholipids - chemistry</topic><topic>Polymers - chemistry</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Thymopentin - chemistry</topic><topic>Thymopentin - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Chengyu</creatorcontrib><creatorcontrib>Zhang, Mengtian</creatorcontrib><creatorcontrib>Zhang, Zhirong</creatorcontrib><creatorcontrib>Wan, Ka-Wai</creatorcontrib><creatorcontrib>Ahmed, Waqar</creatorcontrib><creatorcontrib>Phoenix, David A</creatorcontrib><creatorcontrib>Elhissi, Abdelbary M. A</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Molecular pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Chengyu</au><au>Zhang, Mengtian</au><au>Zhang, Zhirong</au><au>Wan, Ka-Wai</au><au>Ahmed, Waqar</au><au>Phoenix, David A</au><au>Elhissi, Abdelbary M. A</au><au>Sun, Xun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thymopentin Nanoparticles Engineered with High Loading Efficiency, Improved Pharmacokinetic Properties, and Enhanced Immunostimulating Effect Using Soybean Phospholipid and PHBHHx Polymer</atitle><jtitle>Molecular pharmaceutics</jtitle><addtitle>Mol. Pharmaceutics</addtitle><date>2014-10-06</date><risdate>2014</risdate><volume>11</volume><issue>10</issue><spage>3371</spage><epage>3377</epage><pages>3371-3377</pages><issn>1543-8384</issn><eissn>1543-8392</eissn><abstract>Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, −32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>24641274</pmid><doi>10.1021/mp400722r</doi><tpages>7</tpages></addata></record> |
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| subjects | Adjuvants, Immunologic - chemistry Animals Glycine max - chemistry Male Nanoparticles - chemistry Phospholipids - chemistry Polymers - chemistry Rats Rats, Wistar Thymopentin - chemistry Thymopentin - immunology |
| title | Thymopentin Nanoparticles Engineered with High Loading Efficiency, Improved Pharmacokinetic Properties, and Enhanced Immunostimulating Effect Using Soybean Phospholipid and PHBHHx Polymer |
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