Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis
Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is l...
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| Veröffentlicht in: | Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2020-02, Vol.8 (5), p.928-934 |
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| creator | Mao, Jinzhu Wang, Hua Xie, Ying Fu, Yangxue Li, Yuce Liu, Pei Du, Hongyao Zhu, Jinjin Dong, Liyun Hussain, Mubashir Li, Yan Zhang, Lianbin Zhu, Jintao Tao, Juan |
| description | Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion
ex vivo
. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect. |
| doi_str_mv | 10.1039/c9tb00912d |
| format | Article |
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ex vivo
. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect.</description><identifier>ISSN: 2050-750X</identifier><identifier>EISSN: 2050-7518</identifier><identifier>DOI: 10.1039/c9tb00912d</identifier><identifier>PMID: 31912081</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Administration, Cutaneous ; Angiogenesis ; Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - chemistry ; Angiogenesis Inhibitors - pharmacology ; Anomalies ; Antiangiogenics ; Bioavailability ; Cell Proliferation - drug effects ; Cells, Cultured ; Cytotoxicity ; Drug delivery ; Drug Delivery Systems ; Drug development ; Endothelial cells ; Excavation ; Growth factors ; Humans ; Materials Testing ; Mechanical properties ; Needles ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Particle Size ; Polymers - administration & dosage ; Polymers - chemistry ; Polymers - pharmacology ; Polyvinylpyrrolidone ; Rapamycin ; Sirolimus - administration & dosage ; Sirolimus - chemistry ; Sirolimus - pharmacology ; Skin ; Solubility ; Stratum corneum ; Surface Properties ; Toxicity ; Transdermal medication ; Tumors ; Umbilical vein ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - metabolism ; Vascular Malformations - drug therapy ; Vascular Malformations - metabolism ; Vascular Malformations - pathology ; Water - chemistry</subject><ispartof>Journal of materials chemistry. B, Materials for biology and medicine, 2020-02, Vol.8 (5), p.928-934</ispartof><rights>Copyright Royal Society of Chemistry 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-d745e586078ddcb6d49dec5fa6c16f9ad20bdb6c8babf1ea20bbb7dc1e73fc9c3</citedby><cites>FETCH-LOGICAL-c363t-d745e586078ddcb6d49dec5fa6c16f9ad20bdb6c8babf1ea20bbb7dc1e73fc9c3</cites><orcidid>0000-0002-8548-1506 ; 0000-0002-8230-3923 ; 0000-0003-0656-3149</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31912081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Jinzhu</creatorcontrib><creatorcontrib>Wang, Hua</creatorcontrib><creatorcontrib>Xie, Ying</creatorcontrib><creatorcontrib>Fu, Yangxue</creatorcontrib><creatorcontrib>Li, Yuce</creatorcontrib><creatorcontrib>Liu, Pei</creatorcontrib><creatorcontrib>Du, Hongyao</creatorcontrib><creatorcontrib>Zhu, Jinjin</creatorcontrib><creatorcontrib>Dong, Liyun</creatorcontrib><creatorcontrib>Hussain, Mubashir</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Zhang, Lianbin</creatorcontrib><creatorcontrib>Zhu, Jintao</creatorcontrib><creatorcontrib>Tao, Juan</creatorcontrib><title>Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis</title><title>Journal of materials chemistry. B, Materials for biology and medicine</title><addtitle>J Mater Chem B</addtitle><description>Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion
ex vivo
. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect.</description><subject>Administration, Cutaneous</subject><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - chemistry</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Anomalies</subject><subject>Antiangiogenics</subject><subject>Bioavailability</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Cytotoxicity</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Drug development</subject><subject>Endothelial cells</subject><subject>Excavation</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Materials Testing</subject><subject>Mechanical properties</subject><subject>Needles</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Particle Size</subject><subject>Polymers - administration & dosage</subject><subject>Polymers - chemistry</subject><subject>Polymers - pharmacology</subject><subject>Polyvinylpyrrolidone</subject><subject>Rapamycin</subject><subject>Sirolimus - administration & dosage</subject><subject>Sirolimus - chemistry</subject><subject>Sirolimus - pharmacology</subject><subject>Skin</subject><subject>Solubility</subject><subject>Stratum corneum</subject><subject>Surface Properties</subject><subject>Toxicity</subject><subject>Transdermal medication</subject><subject>Tumors</subject><subject>Umbilical vein</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascular Malformations - drug therapy</subject><subject>Vascular Malformations - metabolism</subject><subject>Vascular Malformations - pathology</subject><subject>Water - chemistry</subject><issn>2050-750X</issn><issn>2050-7518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1PGzEQhi3UqqDApXcqIy4V0lJ7nf06QlqgEhKXVOpt5Y9xMPLai72baP99nSakEof6Ys-8z4xm_CL0mZJrSljzTTaDIKShuTpCJzkpSFYVtP5weJPfx-gsxheSTk3Lms0_oWNGU0EKT9BmGbiLCkLHLVZgzRrChL3Ggfe8m6RxeGOGZ9x7H_CGDxCy6O0ojDXDhMWElYkpsTZulRg7dRCMxJ2RwTsAZSFinSq5G0zG3cr4FTiIJp6ij5rbCGf7e4Z-3f1YLh6yx6f7n4ubx0yykg2ZquYFFHVJqlopKUo1bxTIQvNS0lI3XOVEKFHKWnChKfAUClEpSaFiWjaSzdDXXd8--NcR4tB2JkqwljvwY2xzxuYVIUVVJPTyHfrix-DSdIkq0gQ5LbfU1Y5KG8YYQLd9MB0PU0tJu3WkXTTL27-OfE_wl33LUXSgDujb_yfgfAeEKA_qP0uTfvE_ve2VZn8A9ZSfbQ</recordid><startdate>20200207</startdate><enddate>20200207</enddate><creator>Mao, Jinzhu</creator><creator>Wang, Hua</creator><creator>Xie, Ying</creator><creator>Fu, Yangxue</creator><creator>Li, Yuce</creator><creator>Liu, Pei</creator><creator>Du, Hongyao</creator><creator>Zhu, Jinjin</creator><creator>Dong, Liyun</creator><creator>Hussain, Mubashir</creator><creator>Li, Yan</creator><creator>Zhang, Lianbin</creator><creator>Zhu, Jintao</creator><creator>Tao, Juan</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8548-1506</orcidid><orcidid>https://orcid.org/0000-0002-8230-3923</orcidid><orcidid>https://orcid.org/0000-0003-0656-3149</orcidid></search><sort><creationdate>20200207</creationdate><title>Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis</title><author>Mao, Jinzhu ; Wang, Hua ; Xie, Ying ; Fu, Yangxue ; Li, Yuce ; Liu, Pei ; Du, Hongyao ; Zhu, Jinjin ; Dong, Liyun ; Hussain, Mubashir ; Li, Yan ; Zhang, Lianbin ; Zhu, Jintao ; Tao, Juan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-d745e586078ddcb6d49dec5fa6c16f9ad20bdb6c8babf1ea20bbb7dc1e73fc9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Administration, Cutaneous</topic><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - chemistry</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Anomalies</topic><topic>Antiangiogenics</topic><topic>Bioavailability</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Cytotoxicity</topic><topic>Drug delivery</topic><topic>Drug Delivery Systems</topic><topic>Drug development</topic><topic>Endothelial cells</topic><topic>Excavation</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Materials Testing</topic><topic>Mechanical properties</topic><topic>Needles</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Particle Size</topic><topic>Polymers - administration & dosage</topic><topic>Polymers - chemistry</topic><topic>Polymers - pharmacology</topic><topic>Polyvinylpyrrolidone</topic><topic>Rapamycin</topic><topic>Sirolimus - administration & dosage</topic><topic>Sirolimus - chemistry</topic><topic>Sirolimus - pharmacology</topic><topic>Skin</topic><topic>Solubility</topic><topic>Stratum corneum</topic><topic>Surface Properties</topic><topic>Toxicity</topic><topic>Transdermal medication</topic><topic>Tumors</topic><topic>Umbilical vein</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vascular Malformations - drug therapy</topic><topic>Vascular Malformations - metabolism</topic><topic>Vascular Malformations - pathology</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Jinzhu</creatorcontrib><creatorcontrib>Wang, Hua</creatorcontrib><creatorcontrib>Xie, Ying</creatorcontrib><creatorcontrib>Fu, Yangxue</creatorcontrib><creatorcontrib>Li, Yuce</creatorcontrib><creatorcontrib>Liu, Pei</creatorcontrib><creatorcontrib>Du, Hongyao</creatorcontrib><creatorcontrib>Zhu, Jinjin</creatorcontrib><creatorcontrib>Dong, Liyun</creatorcontrib><creatorcontrib>Hussain, Mubashir</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Zhang, Lianbin</creatorcontrib><creatorcontrib>Zhu, Jintao</creatorcontrib><creatorcontrib>Tao, Juan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of materials chemistry. B, Materials for biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Jinzhu</au><au>Wang, Hua</au><au>Xie, Ying</au><au>Fu, Yangxue</au><au>Li, Yuce</au><au>Liu, Pei</au><au>Du, Hongyao</au><au>Zhu, Jinjin</au><au>Dong, Liyun</au><au>Hussain, Mubashir</au><au>Li, Yan</au><au>Zhang, Lianbin</au><au>Zhu, Jintao</au><au>Tao, Juan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis</atitle><jtitle>Journal of materials chemistry. B, Materials for biology and medicine</jtitle><addtitle>J Mater Chem B</addtitle><date>2020-02-07</date><risdate>2020</risdate><volume>8</volume><issue>5</issue><spage>928</spage><epage>934</epage><pages>928-934</pages><issn>2050-750X</issn><eissn>2050-7518</eissn><abstract>Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion
ex vivo
. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>31912081</pmid><doi>10.1039/c9tb00912d</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-8548-1506</orcidid><orcidid>https://orcid.org/0000-0002-8230-3923</orcidid><orcidid>https://orcid.org/0000-0003-0656-3149</orcidid></addata></record> |
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| ispartof | Journal of materials chemistry. B, Materials for biology and medicine, 2020-02, Vol.8 (5), p.928-934 |
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| subjects | Administration, Cutaneous Angiogenesis Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - chemistry Angiogenesis Inhibitors - pharmacology Anomalies Antiangiogenics Bioavailability Cell Proliferation - drug effects Cells, Cultured Cytotoxicity Drug delivery Drug Delivery Systems Drug development Endothelial cells Excavation Growth factors Humans Materials Testing Mechanical properties Needles Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Particle Size Polymers - administration & dosage Polymers - chemistry Polymers - pharmacology Polyvinylpyrrolidone Rapamycin Sirolimus - administration & dosage Sirolimus - chemistry Sirolimus - pharmacology Skin Solubility Stratum corneum Surface Properties Toxicity Transdermal medication Tumors Umbilical vein Vascular endothelial growth factor Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor A - metabolism Vascular Malformations - drug therapy Vascular Malformations - metabolism Vascular Malformations - pathology Water - chemistry |
| title | Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis |
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