Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery
[Display omitted] In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after va...
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Veröffentlicht in: | International journal of pharmaceutics 2020-08, Vol.586, p.119616-119616, Article 119616 |
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container_title | International journal of pharmaceutics |
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creator | Zhang, Sujuan Zhang, Yongtai Wang, Zhi Guo, Teng Hou, Xuefeng He, Zhiyuan He, Zehui Shen, Lina Feng, Nianping |
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In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33 ± 0.91 °C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r > 0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7 days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer. |
doi_str_mv | 10.1016/j.ijpharm.2020.119616 |
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In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33 ± 0.91 °C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r > 0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7 days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2020.119616</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>HeLa ; In situ gel ; Lipid nanoparticles ; SKOV-3</subject><ispartof>International journal of pharmaceutics, 2020-08, Vol.586, p.119616-119616, Article 119616</ispartof><rights>2020 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c342t-360f9c78e8c7d386ca8754931c42e61e8b5111b1769e4f781b79f062165590623</citedby><cites>FETCH-LOGICAL-c342t-360f9c78e8c7d386ca8754931c42e61e8b5111b1769e4f781b79f062165590623</cites><orcidid>0000-0002-9213-7068 ; 0000-0002-5303-2941</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517320306001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Zhang, Sujuan</creatorcontrib><creatorcontrib>Zhang, Yongtai</creatorcontrib><creatorcontrib>Wang, Zhi</creatorcontrib><creatorcontrib>Guo, Teng</creatorcontrib><creatorcontrib>Hou, Xuefeng</creatorcontrib><creatorcontrib>He, Zhiyuan</creatorcontrib><creatorcontrib>He, Zehui</creatorcontrib><creatorcontrib>Shen, Lina</creatorcontrib><creatorcontrib>Feng, Nianping</creatorcontrib><title>Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery</title><title>International journal of pharmaceutics</title><description>[Display omitted]
In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33 ± 0.91 °C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r > 0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7 days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.</description><subject>HeLa</subject><subject>In situ gel</subject><subject>Lipid nanoparticles</subject><subject>SKOV-3</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkM1qwzAQhEVpoWnaRyjo2ItTrWVL9qmU0D8I9JKehSKvEwXbciTFkLevQnrvaZdhZmA-Qh6BLYCBeN4v7H7cad8vcpYnDWoB4orMoJI844UU12TGuKyyEiS_JXch7BljIgc-I4c19iN6HY8es4BDsNFOSLfYZZ3TDTbUuH50SUY66MH12FhjBwy0dZ7GHdLoUcceh0hdSw36yRrdUaOH9NPNiU56a4ekNNilZn-6Jzet7gI-_N05-Xl_Wy8_s9X3x9fydZUZXuQx44K1tZEVVkY2vBJGV7Isag6myFEAVpsSADYgRY1FKyvYyLo9jxJlWafL5-Tp0jt6dzhiiKq3wWDX6QHdMai8yDkTAgqerOXFarwLwWOrRm977U8KmDojVnv1h1idEasL4pR7ueQw7ZgsehWMxTS8sR5NVI2z_zT8AjdBiIg</recordid><startdate>20200830</startdate><enddate>20200830</enddate><creator>Zhang, Sujuan</creator><creator>Zhang, Yongtai</creator><creator>Wang, Zhi</creator><creator>Guo, Teng</creator><creator>Hou, Xuefeng</creator><creator>He, Zhiyuan</creator><creator>He, Zehui</creator><creator>Shen, Lina</creator><creator>Feng, Nianping</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9213-7068</orcidid><orcidid>https://orcid.org/0000-0002-5303-2941</orcidid></search><sort><creationdate>20200830</creationdate><title>Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery</title><author>Zhang, Sujuan ; Zhang, Yongtai ; Wang, Zhi ; Guo, Teng ; Hou, Xuefeng ; He, Zhiyuan ; He, Zehui ; Shen, Lina ; Feng, Nianping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c342t-360f9c78e8c7d386ca8754931c42e61e8b5111b1769e4f781b79f062165590623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>HeLa</topic><topic>In situ gel</topic><topic>Lipid nanoparticles</topic><topic>SKOV-3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Sujuan</creatorcontrib><creatorcontrib>Zhang, Yongtai</creatorcontrib><creatorcontrib>Wang, Zhi</creatorcontrib><creatorcontrib>Guo, Teng</creatorcontrib><creatorcontrib>Hou, Xuefeng</creatorcontrib><creatorcontrib>He, Zhiyuan</creatorcontrib><creatorcontrib>He, Zehui</creatorcontrib><creatorcontrib>Shen, Lina</creatorcontrib><creatorcontrib>Feng, Nianping</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Sujuan</au><au>Zhang, Yongtai</au><au>Wang, Zhi</au><au>Guo, Teng</au><au>Hou, Xuefeng</au><au>He, Zhiyuan</au><au>He, Zehui</au><au>Shen, Lina</au><au>Feng, Nianping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery</atitle><jtitle>International journal of pharmaceutics</jtitle><date>2020-08-30</date><risdate>2020</risdate><volume>586</volume><spage>119616</spage><epage>119616</epage><pages>119616-119616</pages><artnum>119616</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33 ± 0.91 °C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r > 0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7 days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.ijpharm.2020.119616</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9213-7068</orcidid><orcidid>https://orcid.org/0000-0002-5303-2941</orcidid></addata></record> |
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subjects | HeLa In situ gel Lipid nanoparticles SKOV-3 |
title | Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery |
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