Encapsulation of ropivacaine in a combined
Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesi...
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| Veröffentlicht in: | PloS one 2017-10, Vol.12 (10), p.e0185828 |
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| creator | da Silva, Camila Morais Gonçalves Franz-Montan, Michelle Limia, Cíntia Elisabeth Gomez Ribeiro, Lígia Nunes de Morais Braga, Mário Antônio Guilherme, Viviane Aparecida da Silva, Camila Batista Casadei, Bruna Renata Cereda, Cíntia Maria Saia de Paula, Eneida |
| description | Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH.sub.4).sub.2 SO.sub.4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p |
| doi_str_mv | 10.1371/journal.pone.0185828 |
| format | Article |
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The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH.sub.4).sub.2 SO.sub.4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p <0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0185828</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Anesthesia ; Dosage and administration ; Drug delivery systems ; Transmission electron microscopes</subject><ispartof>PloS one, 2017-10, Vol.12 (10), p.e0185828</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>da Silva, Camila Morais Gonçalves</creatorcontrib><creatorcontrib>Franz-Montan, Michelle</creatorcontrib><creatorcontrib>Limia, Cíntia Elisabeth Gomez</creatorcontrib><creatorcontrib>Ribeiro, Lígia Nunes de Morais</creatorcontrib><creatorcontrib>Braga, Mário Antônio</creatorcontrib><creatorcontrib>Guilherme, Viviane Aparecida</creatorcontrib><creatorcontrib>da Silva, Camila Batista</creatorcontrib><creatorcontrib>Casadei, Bruna Renata</creatorcontrib><creatorcontrib>Cereda, Cíntia Maria Saia</creatorcontrib><creatorcontrib>de Paula, Eneida</creatorcontrib><title>Encapsulation of ropivacaine in a combined</title><title>PloS one</title><description>Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH.sub.4).sub.2 SO.sub.4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p <0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time.</description><subject>Anesthesia</subject><subject>Dosage and administration</subject><subject>Drug delivery systems</subject><subject>Transmission electron microscopes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFz8FLwzAUBvAgCs7pf-ChJ0Gh9eXFtslxjE0Hg4EOr-U1TbqOmIylFf98FT3Uk6f3ffDjg8fYNYeMi5Lf78Nw9OSyQ_AmAy5zifKETbgSmBYI4nSUz9lFjHuAXMiimLC7hdd0iIOjvgs-CTY5hkP3Tpo6b5LOJ5To8FZ_leaSnVly0Vz93inbLhfb-VO63jyu5rN12irFUyEkgNW1ahqhdGkFlLa2qkCqwSCSlqhraQiw4Jgjas0pVyhVY-GBF6WYstuf2ZacqTqvg-_NR9_SEGO1enmuZjlIBKkE_8duXv_am5HdGXL9LgY3fP8dx_ATMORiCw</recordid><startdate>20171005</startdate><enddate>20171005</enddate><creator>da Silva, Camila Morais Gonçalves</creator><creator>Franz-Montan, Michelle</creator><creator>Limia, Cíntia Elisabeth Gomez</creator><creator>Ribeiro, Lígia Nunes de Morais</creator><creator>Braga, Mário Antônio</creator><creator>Guilherme, Viviane Aparecida</creator><creator>da Silva, Camila Batista</creator><creator>Casadei, Bruna Renata</creator><creator>Cereda, Cíntia Maria Saia</creator><creator>de Paula, Eneida</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20171005</creationdate><title>Encapsulation of ropivacaine in a combined</title><author>da Silva, Camila Morais Gonçalves ; Franz-Montan, Michelle ; Limia, Cíntia Elisabeth Gomez ; Ribeiro, Lígia Nunes de Morais ; Braga, Mário Antônio ; Guilherme, Viviane Aparecida ; da Silva, Camila Batista ; Casadei, Bruna Renata ; Cereda, Cíntia Maria Saia ; de Paula, Eneida</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g991-33800fcb9dd39c7f307fbf962ab0e22ac82cb8ea02612522cc1a59289df041673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anesthesia</topic><topic>Dosage and administration</topic><topic>Drug delivery systems</topic><topic>Transmission electron microscopes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>da Silva, Camila Morais Gonçalves</creatorcontrib><creatorcontrib>Franz-Montan, Michelle</creatorcontrib><creatorcontrib>Limia, Cíntia Elisabeth Gomez</creatorcontrib><creatorcontrib>Ribeiro, Lígia Nunes de Morais</creatorcontrib><creatorcontrib>Braga, Mário Antônio</creatorcontrib><creatorcontrib>Guilherme, Viviane Aparecida</creatorcontrib><creatorcontrib>da Silva, Camila Batista</creatorcontrib><creatorcontrib>Casadei, Bruna Renata</creatorcontrib><creatorcontrib>Cereda, Cíntia Maria Saia</creatorcontrib><creatorcontrib>de Paula, Eneida</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>da Silva, Camila Morais Gonçalves</au><au>Franz-Montan, Michelle</au><au>Limia, Cíntia Elisabeth Gomez</au><au>Ribeiro, Lígia Nunes de Morais</au><au>Braga, Mário Antônio</au><au>Guilherme, Viviane Aparecida</au><au>da Silva, Camila Batista</au><au>Casadei, Bruna Renata</au><au>Cereda, Cíntia Maria Saia</au><au>de Paula, Eneida</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Encapsulation of ropivacaine in a combined</atitle><jtitle>PloS one</jtitle><date>2017-10-05</date><risdate>2017</risdate><volume>12</volume><issue>10</issue><spage>e0185828</spage><pages>e0185828-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH.sub.4).sub.2 SO.sub.4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p <0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0185828</doi><tpages>e0185828</tpages></addata></record> |
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| subjects | Anesthesia Dosage and administration Drug delivery systems Transmission electron microscopes |
| title | Encapsulation of ropivacaine in a combined |
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