A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis
To effectively alleviate acute severe ulcerative colitis (ASUC), we developed a colon-specific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). The lysine-proline-valine (KPV) tripeptide, which possesses anti-inflammatory properties and high a...
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| Veröffentlicht in: | Biomaterials science 2019-10, Vol.7 (1), p.4299-439 |
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| creator | Wu, Ya Sun, Minghui Wang, Dan Li, Genyun Huang, Jiangeng Tan, Songwei Bao, Lin Li, Qian Li, Gao Si, Luqin |
| description | To effectively alleviate acute severe ulcerative colitis (ASUC), we developed a colon-specific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). The lysine-proline-valine (KPV) tripeptide, which possesses anti-inflammatory properties and high affinity to peptide transporter 1 (PepT1), can target therapy-related cells (colonic epithelial cells and macrophages)
via
overexpression of PepT1. Montmorillonite (MMT)/chitosan (CS) coating can reduce CyA leakage in the upper gastrointestinal tract (GIT) and enhance nanoparticle adhesion to the inflamed colon. The bio-distribution demonstrated that nanoparticles can specifically accumulate in the inflamed tissues and can be retained for up to 36 h. After being treated with the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN), the mice with DSS-induced ulcerative colitis exhibited significant improvements in body weight, colon length, and disease activity index. Moreover, biochemistry and immunohistochemical analysis showed that the PKMCN treatment group performed as well as the healthy group. Intriguingly, PKMCN without CyA also presented marked therapeutic effects. Our results suggested that PKMCN could be a promising drug delivery system for ASUC therapy by targeting inflamed cells, prolonging curative time, and mitigating colitis.
A novel nano-system (PKMCN) with medical value could accumulate in the inflamed colon tissues and exhibit a strong anti-inflammatory effect. |
| doi_str_mv | 10.1039/c9bm00925f |
| format | Article |
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via
overexpression of PepT1. Montmorillonite (MMT)/chitosan (CS) coating can reduce CyA leakage in the upper gastrointestinal tract (GIT) and enhance nanoparticle adhesion to the inflamed colon. The bio-distribution demonstrated that nanoparticles can specifically accumulate in the inflamed tissues and can be retained for up to 36 h. After being treated with the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN), the mice with DSS-induced ulcerative colitis exhibited significant improvements in body weight, colon length, and disease activity index. Moreover, biochemistry and immunohistochemical analysis showed that the PKMCN treatment group performed as well as the healthy group. Intriguingly, PKMCN without CyA also presented marked therapeutic effects. Our results suggested that PKMCN could be a promising drug delivery system for ASUC therapy by targeting inflamed cells, prolonging curative time, and mitigating colitis.
A novel nano-system (PKMCN) with medical value could accumulate in the inflamed colon tissues and exhibit a strong anti-inflammatory effect.</description><identifier>ISSN: 2047-4830</identifier><identifier>EISSN: 2047-4849</identifier><identifier>DOI: 10.1039/c9bm00925f</identifier><identifier>PMID: 31408067</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject><![CDATA[Animals ; Anti-Inflammatory Agents - administration & dosage ; Anti-Inflammatory Agents - chemistry ; Body weight ; Chitosan ; Colitis, Ulcerative - chemically induced ; Colitis, Ulcerative - drug therapy ; Colitis, Ulcerative - metabolism ; Colitis, Ulcerative - pathology ; Colon ; Colon - drug effects ; Colon - pathology ; Cyclosporine - administration & dosage ; Cyclosporine - chemistry ; Dextran Sulfate ; Drug Carriers - administration & dosage ; Drug Carriers - chemistry ; Drug delivery systems ; Gastrointestinal system ; Inflammatory bowel disease ; Lysine ; Macrophages ; Male ; Mice, Inbred BALB C ; Montmorillonite ; Nanoparticles ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Oligopeptides - administration & dosage ; Oligopeptides - chemistry ; Peptide Transporter 1 - metabolism ; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage ; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry ; Proline ; Therapy ; Valine]]></subject><ispartof>Biomaterials science, 2019-10, Vol.7 (1), p.4299-439</ispartof><rights>Copyright Royal Society of Chemistry 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-19d2427dc92d6f38dfe5557cf338bcc96f88f68b01dc710c49868c94a3a45f523</citedby><cites>FETCH-LOGICAL-c378t-19d2427dc92d6f38dfe5557cf338bcc96f88f68b01dc710c49868c94a3a45f523</cites><orcidid>0000-0002-0224-2922 ; 0000-0002-2986-8968 ; 0000-0001-9298-2467</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31408067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Ya</creatorcontrib><creatorcontrib>Sun, Minghui</creatorcontrib><creatorcontrib>Wang, Dan</creatorcontrib><creatorcontrib>Li, Genyun</creatorcontrib><creatorcontrib>Huang, Jiangeng</creatorcontrib><creatorcontrib>Tan, Songwei</creatorcontrib><creatorcontrib>Bao, Lin</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Li, Gao</creatorcontrib><creatorcontrib>Si, Luqin</creatorcontrib><title>A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis</title><title>Biomaterials science</title><addtitle>Biomater Sci</addtitle><description>To effectively alleviate acute severe ulcerative colitis (ASUC), we developed a colon-specific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). The lysine-proline-valine (KPV) tripeptide, which possesses anti-inflammatory properties and high affinity to peptide transporter 1 (PepT1), can target therapy-related cells (colonic epithelial cells and macrophages)
via
overexpression of PepT1. Montmorillonite (MMT)/chitosan (CS) coating can reduce CyA leakage in the upper gastrointestinal tract (GIT) and enhance nanoparticle adhesion to the inflamed colon. The bio-distribution demonstrated that nanoparticles can specifically accumulate in the inflamed tissues and can be retained for up to 36 h. After being treated with the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN), the mice with DSS-induced ulcerative colitis exhibited significant improvements in body weight, colon length, and disease activity index. Moreover, biochemistry and immunohistochemical analysis showed that the PKMCN treatment group performed as well as the healthy group. Intriguingly, PKMCN without CyA also presented marked therapeutic effects. Our results suggested that PKMCN could be a promising drug delivery system for ASUC therapy by targeting inflamed cells, prolonging curative time, and mitigating colitis.
A novel nano-system (PKMCN) with medical value could accumulate in the inflamed colon tissues and exhibit a strong anti-inflammatory effect.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Body weight</subject><subject>Chitosan</subject><subject>Colitis, Ulcerative - chemically induced</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colitis, Ulcerative - metabolism</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Colon</subject><subject>Colon - drug effects</subject><subject>Colon - pathology</subject><subject>Cyclosporine - administration & dosage</subject><subject>Cyclosporine - chemistry</subject><subject>Dextran Sulfate</subject><subject>Drug Carriers - administration & dosage</subject><subject>Drug Carriers - chemistry</subject><subject>Drug delivery systems</subject><subject>Gastrointestinal system</subject><subject>Inflammatory bowel disease</subject><subject>Lysine</subject><subject>Macrophages</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Montmorillonite</subject><subject>Nanoparticles</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Oligopeptides - administration & dosage</subject><subject>Oligopeptides - chemistry</subject><subject>Peptide Transporter 1 - metabolism</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</subject><subject>Proline</subject><subject>Therapy</subject><subject>Valine</subject><issn>2047-4830</issn><issn>2047-4849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkd9LwzAQx4MoTuZefFcCvgnVpEnb5HEOp8JEH-ZzSa-JdLTNTNpB8Z83--G8h7uD-9wX7nsIXVFyTwmTDyCLhhAZJ-YEXcSEZxEXXJ4ee0ZGaOL9ioTIMklSeo5GjHIiSJpdoJ8p_tDrJcWNLivV6XLXQNWqGreqtZEffKcbbKzDnXJfeouUuq422g3YGgwD1Navratajae4s1jVtd5stbCCPmSvA6txX4N2qguLGGxddZW_RGdG1V5PDnWMPudPy9lLtHh_fp1NFxGwTHQRlWXM46wEGZepYaI0OkmSDAxjogCQqRHCpKIgtISMEuBSpAIkV0zxxCQxG6Pbve7a2e9e-y5f2d6FC30exzKlCaGcB-puT4Gz3jtt8rWrGuWGnJJ8a3U-k49vO6vnAb45SPZFMOyI_hkbgOs94Dwcp_-_Yr_D4IPj</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Wu, Ya</creator><creator>Sun, Minghui</creator><creator>Wang, Dan</creator><creator>Li, Genyun</creator><creator>Huang, Jiangeng</creator><creator>Tan, Songwei</creator><creator>Bao, Lin</creator><creator>Li, Qian</creator><creator>Li, Gao</creator><creator>Si, Luqin</creator><general>Royal Society of Chemistry</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><orcidid>https://orcid.org/0000-0002-0224-2922</orcidid><orcidid>https://orcid.org/0000-0002-2986-8968</orcidid><orcidid>https://orcid.org/0000-0001-9298-2467</orcidid></search><sort><creationdate>20191001</creationdate><title>A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis</title><author>Wu, Ya ; Sun, Minghui ; Wang, Dan ; Li, Genyun ; Huang, Jiangeng ; Tan, Songwei ; Bao, Lin ; Li, Qian ; Li, Gao ; Si, Luqin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-19d2427dc92d6f38dfe5557cf338bcc96f88f68b01dc710c49868c94a3a45f523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Body weight</topic><topic>Chitosan</topic><topic>Colitis, Ulcerative - chemically induced</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colitis, Ulcerative - metabolism</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Colon</topic><topic>Colon - drug effects</topic><topic>Colon - pathology</topic><topic>Cyclosporine - administration & dosage</topic><topic>Cyclosporine - chemistry</topic><topic>Dextran Sulfate</topic><topic>Drug Carriers - administration & dosage</topic><topic>Drug Carriers - chemistry</topic><topic>Drug delivery systems</topic><topic>Gastrointestinal system</topic><topic>Inflammatory bowel disease</topic><topic>Lysine</topic><topic>Macrophages</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Montmorillonite</topic><topic>Nanoparticles</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Oligopeptides - administration & dosage</topic><topic>Oligopeptides - chemistry</topic><topic>Peptide Transporter 1 - metabolism</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</topic><topic>Proline</topic><topic>Therapy</topic><topic>Valine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Ya</creatorcontrib><creatorcontrib>Sun, Minghui</creatorcontrib><creatorcontrib>Wang, Dan</creatorcontrib><creatorcontrib>Li, Genyun</creatorcontrib><creatorcontrib>Huang, Jiangeng</creatorcontrib><creatorcontrib>Tan, Songwei</creatorcontrib><creatorcontrib>Bao, Lin</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Li, Gao</creatorcontrib><creatorcontrib>Si, Luqin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><jtitle>Biomaterials science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Ya</au><au>Sun, Minghui</au><au>Wang, Dan</au><au>Li, Genyun</au><au>Huang, Jiangeng</au><au>Tan, Songwei</au><au>Bao, Lin</au><au>Li, Qian</au><au>Li, Gao</au><au>Si, Luqin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis</atitle><jtitle>Biomaterials science</jtitle><addtitle>Biomater Sci</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>7</volume><issue>1</issue><spage>4299</spage><epage>439</epage><pages>4299-439</pages><issn>2047-4830</issn><eissn>2047-4849</eissn><abstract>To effectively alleviate acute severe ulcerative colitis (ASUC), we developed a colon-specific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). The lysine-proline-valine (KPV) tripeptide, which possesses anti-inflammatory properties and high affinity to peptide transporter 1 (PepT1), can target therapy-related cells (colonic epithelial cells and macrophages)
via
overexpression of PepT1. Montmorillonite (MMT)/chitosan (CS) coating can reduce CyA leakage in the upper gastrointestinal tract (GIT) and enhance nanoparticle adhesion to the inflamed colon. The bio-distribution demonstrated that nanoparticles can specifically accumulate in the inflamed tissues and can be retained for up to 36 h. After being treated with the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN), the mice with DSS-induced ulcerative colitis exhibited significant improvements in body weight, colon length, and disease activity index. Moreover, biochemistry and immunohistochemical analysis showed that the PKMCN treatment group performed as well as the healthy group. Intriguingly, PKMCN without CyA also presented marked therapeutic effects. Our results suggested that PKMCN could be a promising drug delivery system for ASUC therapy by targeting inflamed cells, prolonging curative time, and mitigating colitis.
A novel nano-system (PKMCN) with medical value could accumulate in the inflamed colon tissues and exhibit a strong anti-inflammatory effect.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>31408067</pmid><doi>10.1039/c9bm00925f</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0224-2922</orcidid><orcidid>https://orcid.org/0000-0002-2986-8968</orcidid><orcidid>https://orcid.org/0000-0001-9298-2467</orcidid></addata></record> |
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| source | MEDLINE; Royal Society Of Chemistry Journals 2008- |
| subjects | Animals Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - chemistry Body weight Chitosan Colitis, Ulcerative - chemically induced Colitis, Ulcerative - drug therapy Colitis, Ulcerative - metabolism Colitis, Ulcerative - pathology Colon Colon - drug effects Colon - pathology Cyclosporine - administration & dosage Cyclosporine - chemistry Dextran Sulfate Drug Carriers - administration & dosage Drug Carriers - chemistry Drug delivery systems Gastrointestinal system Inflammatory bowel disease Lysine Macrophages Male Mice, Inbred BALB C Montmorillonite Nanoparticles Nanoparticles - administration & dosage Nanoparticles - chemistry Oligopeptides - administration & dosage Oligopeptides - chemistry Peptide Transporter 1 - metabolism Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Proline Therapy Valine |
| title | A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis |
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