Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo
[Display omitted] •Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal adm...
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| Veröffentlicht in: | International journal of pharmaceutics 2022-03, Vol.616, p.121563-121563, Article 121563 |
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| container_title | International journal of pharmaceutics |
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| creator | Bruinsmann, Franciele Aline de Cristo Soares Alves, Aline de Fraga Dias, Amanda Lopes Silva, Luiz Fernando Visioli, Fernanda Raffin Pohlmann, Adriana Figueiró, Fabrício Sonvico, Fabio Stanisçuaski Guterres, Silvia |
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•Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal administration.•LNCSVT-chit treatment decreased the tumor size and malignancy in glioblastoma-bearing rats.
Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNCSVT-chit) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI |
| doi_str_mv | 10.1016/j.ijpharm.2022.121563 |
| format | Article |
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•Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal administration.•LNCSVT-chit treatment decreased the tumor size and malignancy in glioblastoma-bearing rats.
Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNCSVT-chit) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI < 0.2), positive zeta potential and high encapsulation efficiency (nearly 100%). In vitro cytotoxicity of LNCSVT-chit was comparable to non-encapsulated SVT in C6 rat glioma cells, whereas LNCSVT-chit were more cytotoxic than non-encapsulated SVT after 72 h of incubation against U-138 MG human glioblastoma cell line. In studies carried out in rats, LNCSVT-chit significantly enhanced the amount of drug in rat brain tissue after intranasal administration (2.4-fold) when compared with free SVT. Moreover, LNCSVT-chit promoted a significant decrease in tumor growth and malignancy in glioma-bearing rats in comparison to control and free SVT groups. Additionally, LNCSVT-chit did not cause any toxicity in treated rats. Considered overall, the results demonstrated that the nose-to-brain administration of LNCSVT-chit represents a novel potential strategy for glioblastoma treatment.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2022.121563</identifier><identifier>PMID: 35151819</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Administration, Intranasal ; Animals ; Brain - metabolism ; Cell Line, Tumor ; Chitosan ; Chitosan - therapeutic use ; Glioblastoma ; Glioblastoma - drug therapy ; Glioblastoma - metabolism ; Intranasal administration ; Lipids ; Nanocapsules ; Nose-to-brain delivery ; Rats ; Simvastatin</subject><ispartof>International journal of pharmaceutics, 2022-03, Vol.616, p.121563-121563, Article 121563</ispartof><rights>2022</rights><rights>Copyright © 2022. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-6784e177812daa7d5a76eabf1590cbf5c4b126bd84e21e7e936d3e38a2d701c33</citedby><cites>FETCH-LOGICAL-c365t-6784e177812daa7d5a76eabf1590cbf5c4b126bd84e21e7e936d3e38a2d701c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2022.121563$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35151819$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bruinsmann, Franciele Aline</creatorcontrib><creatorcontrib>de Cristo Soares Alves, Aline</creatorcontrib><creatorcontrib>de Fraga Dias, Amanda</creatorcontrib><creatorcontrib>Lopes Silva, Luiz Fernando</creatorcontrib><creatorcontrib>Visioli, Fernanda</creatorcontrib><creatorcontrib>Raffin Pohlmann, Adriana</creatorcontrib><creatorcontrib>Figueiró, Fabrício</creatorcontrib><creatorcontrib>Sonvico, Fabio</creatorcontrib><creatorcontrib>Stanisçuaski Guterres, Silvia</creatorcontrib><title>Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
•Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal administration.•LNCSVT-chit treatment decreased the tumor size and malignancy in glioblastoma-bearing rats.
Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNCSVT-chit) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI < 0.2), positive zeta potential and high encapsulation efficiency (nearly 100%). In vitro cytotoxicity of LNCSVT-chit was comparable to non-encapsulated SVT in C6 rat glioma cells, whereas LNCSVT-chit were more cytotoxic than non-encapsulated SVT after 72 h of incubation against U-138 MG human glioblastoma cell line. In studies carried out in rats, LNCSVT-chit significantly enhanced the amount of drug in rat brain tissue after intranasal administration (2.4-fold) when compared with free SVT. Moreover, LNCSVT-chit promoted a significant decrease in tumor growth and malignancy in glioma-bearing rats in comparison to control and free SVT groups. Additionally, LNCSVT-chit did not cause any toxicity in treated rats. Considered overall, the results demonstrated that the nose-to-brain administration of LNCSVT-chit represents a novel potential strategy for glioblastoma treatment.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chitosan</subject><subject>Chitosan - therapeutic use</subject><subject>Glioblastoma</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - metabolism</subject><subject>Intranasal administration</subject><subject>Lipids</subject><subject>Nanocapsules</subject><subject>Nose-to-brain delivery</subject><subject>Rats</subject><subject>Simvastatin</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYsLAJ4C8ZNPBj9jurBAaDQ9pBBtYW9V2NXHkbgfbaZRf4KtxSGDLqlSlU7dU9xLykrM1Z1y_2a_D_rCDPK0FE2LNBVdaPiIr3hvZyY3Rj8mKSdN3iht5Q56VsmeMacHlU3IjFVe859sV-fU5Fexq6oYMYaYeY1gwn2gaaQnTAqVCbfMJfYCKng4n6nahpgJz59KfUQyH4FuTkc4wJweHcoxYKMSYfhY6pkzrDmnNCHXCuZ61v8eQhtjU0wS06S9hSc_JkxFiwRfXeku-vb__evexe_jy4dPdu4fOSa1qp02_QW5Mz4UHMF6B0QjDyNWWuWFUbjNwoQffKMHR4FZqL1H2ILxh3El5S15fdA85_ThiqXYKxWGMMGM6Fiu06LVptqmGqgvqciol42gPOUyQT5Yze47B7u01BnuOwV5iaHuvrieOQ7Pu39Zf3xvw9gJge3QJmG1xAWfXbM7oqvUp_OfEb9l_nsw</recordid><startdate>20220325</startdate><enddate>20220325</enddate><creator>Bruinsmann, Franciele Aline</creator><creator>de Cristo Soares Alves, Aline</creator><creator>de Fraga Dias, Amanda</creator><creator>Lopes Silva, Luiz Fernando</creator><creator>Visioli, Fernanda</creator><creator>Raffin Pohlmann, Adriana</creator><creator>Figueiró, Fabrício</creator><creator>Sonvico, Fabio</creator><creator>Stanisçuaski Guterres, Silvia</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20220325</creationdate><title>Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo</title><author>Bruinsmann, Franciele Aline ; de Cristo Soares Alves, Aline ; de Fraga Dias, Amanda ; Lopes Silva, Luiz Fernando ; Visioli, Fernanda ; Raffin Pohlmann, Adriana ; Figueiró, Fabrício ; Sonvico, Fabio ; Stanisçuaski Guterres, Silvia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-6784e177812daa7d5a76eabf1590cbf5c4b126bd84e21e7e936d3e38a2d701c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Administration, Intranasal</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chitosan</topic><topic>Chitosan - therapeutic use</topic><topic>Glioblastoma</topic><topic>Glioblastoma - drug therapy</topic><topic>Glioblastoma - metabolism</topic><topic>Intranasal administration</topic><topic>Lipids</topic><topic>Nanocapsules</topic><topic>Nose-to-brain delivery</topic><topic>Rats</topic><topic>Simvastatin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bruinsmann, Franciele Aline</creatorcontrib><creatorcontrib>de Cristo Soares Alves, Aline</creatorcontrib><creatorcontrib>de Fraga Dias, Amanda</creatorcontrib><creatorcontrib>Lopes Silva, Luiz Fernando</creatorcontrib><creatorcontrib>Visioli, Fernanda</creatorcontrib><creatorcontrib>Raffin Pohlmann, Adriana</creatorcontrib><creatorcontrib>Figueiró, Fabrício</creatorcontrib><creatorcontrib>Sonvico, Fabio</creatorcontrib><creatorcontrib>Stanisçuaski Guterres, Silvia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><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>Bruinsmann, Franciele Aline</au><au>de Cristo Soares Alves, Aline</au><au>de Fraga Dias, Amanda</au><au>Lopes Silva, Luiz Fernando</au><au>Visioli, Fernanda</au><au>Raffin Pohlmann, Adriana</au><au>Figueiró, Fabrício</au><au>Sonvico, Fabio</au><au>Stanisçuaski Guterres, Silvia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2022-03-25</date><risdate>2022</risdate><volume>616</volume><spage>121563</spage><epage>121563</epage><pages>121563-121563</pages><artnum>121563</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
•Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal administration.•LNCSVT-chit treatment decreased the tumor size and malignancy in glioblastoma-bearing rats.
Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNCSVT-chit) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI < 0.2), positive zeta potential and high encapsulation efficiency (nearly 100%). In vitro cytotoxicity of LNCSVT-chit was comparable to non-encapsulated SVT in C6 rat glioma cells, whereas LNCSVT-chit were more cytotoxic than non-encapsulated SVT after 72 h of incubation against U-138 MG human glioblastoma cell line. In studies carried out in rats, LNCSVT-chit significantly enhanced the amount of drug in rat brain tissue after intranasal administration (2.4-fold) when compared with free SVT. Moreover, LNCSVT-chit promoted a significant decrease in tumor growth and malignancy in glioma-bearing rats in comparison to control and free SVT groups. Additionally, LNCSVT-chit did not cause any toxicity in treated rats. Considered overall, the results demonstrated that the nose-to-brain administration of LNCSVT-chit represents a novel potential strategy for glioblastoma treatment.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>35151819</pmid><doi>10.1016/j.ijpharm.2022.121563</doi><tpages>1</tpages></addata></record> |
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| subjects | Administration, Intranasal Animals Brain - metabolism Cell Line, Tumor Chitosan Chitosan - therapeutic use Glioblastoma Glioblastoma - drug therapy Glioblastoma - metabolism Intranasal administration Lipids Nanocapsules Nose-to-brain delivery Rats Simvastatin |
| title | Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo |
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