Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis
This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX...
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| Veröffentlicht in: | European journal of pharmaceutical sciences 2021-08, Vol.163, p.105856-105856, Article 105856 |
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| creator | Agostini, Sandra Barbosa Neder Malta, Iago Henrique Silva Rodrigues, Rafaela Figueiredo Freitas, Jennifer Tavares Jacon Lino, Mônica Esselin de Sousa dos Santos, Rafaela Silva Elisei, Lívia Silvestre Moraes, Thamyris Reis Giusto, Luana Aparecida dos Reis de Oliveira, Merelym Ketterym Bassi da Silva, Jéssica Bruschi, Marcos Luciano Santos, Aline Martins dos Nogueira, Denismar Alves Novaes, Rômulo Dias Pereira, Gislaine Ribeiro Galdino, Giovane Carvalho, Flávia Chiva |
| description | This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug. |
| doi_str_mv | 10.1016/j.ejps.2021.105856 |
| format | Article |
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MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2021.105856</identifier><identifier>PMID: 33882329</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Chitooligosaccharide ; Chitosan ; Drug delivery system ; Hypromellose phthalate ; Methotrexate ; Polyelectrolyte complexes ; Rheumatoid arthritis</subject><ispartof>European journal of pharmaceutical sciences, 2021-08, Vol.163, p.105856-105856, Article 105856</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-e9bbcee8ce30400fc3da56450ebc8e42855397a8123df25759cdb87d147ae36e3</citedby><cites>FETCH-LOGICAL-c356t-e9bbcee8ce30400fc3da56450ebc8e42855397a8123df25759cdb87d147ae36e3</cites><orcidid>0000-0001-7586-539X ; 0000-0003-0483-3678 ; 0000-0003-2293-7868 ; 0000-0002-4838-5742</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejps.2021.105856$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33882329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Agostini, Sandra Barbosa Neder</creatorcontrib><creatorcontrib>Malta, Iago Henrique Silva</creatorcontrib><creatorcontrib>Rodrigues, Rafaela Figueiredo</creatorcontrib><creatorcontrib>Freitas, Jennifer Tavares Jacon</creatorcontrib><creatorcontrib>Lino, Mônica Esselin de Sousa</creatorcontrib><creatorcontrib>dos Santos, Rafaela Silva</creatorcontrib><creatorcontrib>Elisei, Lívia Silvestre</creatorcontrib><creatorcontrib>Moraes, Thamyris Reis</creatorcontrib><creatorcontrib>Giusto, Luana Aparecida dos Reis</creatorcontrib><creatorcontrib>de Oliveira, Merelym Ketterym</creatorcontrib><creatorcontrib>Bassi da Silva, Jéssica</creatorcontrib><creatorcontrib>Bruschi, Marcos Luciano</creatorcontrib><creatorcontrib>Santos, Aline Martins dos</creatorcontrib><creatorcontrib>Nogueira, Denismar Alves</creatorcontrib><creatorcontrib>Novaes, Rômulo Dias</creatorcontrib><creatorcontrib>Pereira, Gislaine Ribeiro</creatorcontrib><creatorcontrib>Galdino, Giovane</creatorcontrib><creatorcontrib>Carvalho, Flávia Chiva</creatorcontrib><title>Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.</description><subject>Chitooligosaccharide</subject><subject>Chitosan</subject><subject>Drug delivery system</subject><subject>Hypromellose phthalate</subject><subject>Methotrexate</subject><subject>Polyelectrolyte complexes</subject><subject>Rheumatoid arthritis</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EotPCC7BAXrLJ1D9x4khsqqq0lSrBAtaWY98Qj5w42M5o5hl4aTya0mVX9-rec87ifAh9omRLCW2ud1vYLWnLCKPlIKRo3qANlW1XkZaRt2hDOiYr0sn2Al2mtCOENLIl79EF51IyzroN-vsjgvFudkZ7DHvtV51dmHEY8AR5DDnCQWeofNAWLF6CP4IHk2NZMmATpsXDARLWs8V5hDiFBHNy2e0Bj0cbw2_w5ZtwSdJ5gjnjIUQcR1gnnYOzWMc8xmJIH9C7QfsEH5_nFfr17e7n7UP19P3-8fbmqTJcNLmCru8NgDTASU3IYLjVoqkFgd5IqJkUgnetlpRxOzDRis7YXraW1q0G3gC_Ql_OuUsMf1ZIWU0uGfBezxDWpJigjax5TXiRsrPUxJBShEEt0U06HhUl6gRB7dQJgjpBUGcIxfT5OX_tJ7Avlv-tF8HXs6BUA3sHUSXjYDZgXaGRlQ3utfx_Wz2dsg</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Agostini, Sandra Barbosa Neder</creator><creator>Malta, Iago Henrique Silva</creator><creator>Rodrigues, Rafaela Figueiredo</creator><creator>Freitas, Jennifer Tavares Jacon</creator><creator>Lino, Mônica Esselin de Sousa</creator><creator>dos Santos, Rafaela Silva</creator><creator>Elisei, Lívia Silvestre</creator><creator>Moraes, Thamyris Reis</creator><creator>Giusto, Luana Aparecida dos Reis</creator><creator>de Oliveira, Merelym Ketterym</creator><creator>Bassi da Silva, Jéssica</creator><creator>Bruschi, Marcos Luciano</creator><creator>Santos, Aline Martins dos</creator><creator>Nogueira, Denismar Alves</creator><creator>Novaes, Rômulo Dias</creator><creator>Pereira, Gislaine Ribeiro</creator><creator>Galdino, Giovane</creator><creator>Carvalho, Flávia Chiva</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7586-539X</orcidid><orcidid>https://orcid.org/0000-0003-0483-3678</orcidid><orcidid>https://orcid.org/0000-0003-2293-7868</orcidid><orcidid>https://orcid.org/0000-0002-4838-5742</orcidid></search><sort><creationdate>20210801</creationdate><title>Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis</title><author>Agostini, Sandra Barbosa Neder ; Malta, Iago Henrique Silva ; Rodrigues, Rafaela Figueiredo ; Freitas, Jennifer Tavares Jacon ; Lino, Mônica Esselin de Sousa ; dos Santos, Rafaela Silva ; Elisei, Lívia Silvestre ; Moraes, Thamyris Reis ; Giusto, Luana Aparecida dos Reis ; de Oliveira, Merelym Ketterym ; Bassi da Silva, Jéssica ; Bruschi, Marcos Luciano ; Santos, Aline Martins dos ; Nogueira, Denismar Alves ; Novaes, Rômulo Dias ; Pereira, Gislaine Ribeiro ; Galdino, Giovane ; Carvalho, Flávia Chiva</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-e9bbcee8ce30400fc3da56450ebc8e42855397a8123df25759cdb87d147ae36e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Chitooligosaccharide</topic><topic>Chitosan</topic><topic>Drug delivery system</topic><topic>Hypromellose phthalate</topic><topic>Methotrexate</topic><topic>Polyelectrolyte complexes</topic><topic>Rheumatoid arthritis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Agostini, Sandra Barbosa Neder</creatorcontrib><creatorcontrib>Malta, Iago Henrique Silva</creatorcontrib><creatorcontrib>Rodrigues, Rafaela Figueiredo</creatorcontrib><creatorcontrib>Freitas, Jennifer Tavares Jacon</creatorcontrib><creatorcontrib>Lino, Mônica Esselin de Sousa</creatorcontrib><creatorcontrib>dos Santos, Rafaela Silva</creatorcontrib><creatorcontrib>Elisei, Lívia Silvestre</creatorcontrib><creatorcontrib>Moraes, Thamyris Reis</creatorcontrib><creatorcontrib>Giusto, Luana Aparecida dos Reis</creatorcontrib><creatorcontrib>de Oliveira, Merelym Ketterym</creatorcontrib><creatorcontrib>Bassi da Silva, Jéssica</creatorcontrib><creatorcontrib>Bruschi, Marcos Luciano</creatorcontrib><creatorcontrib>Santos, Aline Martins dos</creatorcontrib><creatorcontrib>Nogueira, Denismar Alves</creatorcontrib><creatorcontrib>Novaes, Rômulo Dias</creatorcontrib><creatorcontrib>Pereira, Gislaine Ribeiro</creatorcontrib><creatorcontrib>Galdino, Giovane</creatorcontrib><creatorcontrib>Carvalho, Flávia Chiva</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Agostini, Sandra Barbosa Neder</au><au>Malta, Iago Henrique Silva</au><au>Rodrigues, Rafaela Figueiredo</au><au>Freitas, Jennifer Tavares Jacon</au><au>Lino, Mônica Esselin de Sousa</au><au>dos Santos, Rafaela Silva</au><au>Elisei, Lívia Silvestre</au><au>Moraes, Thamyris Reis</au><au>Giusto, Luana Aparecida dos Reis</au><au>de Oliveira, Merelym Ketterym</au><au>Bassi da Silva, Jéssica</au><au>Bruschi, Marcos Luciano</au><au>Santos, Aline Martins dos</au><au>Nogueira, Denismar Alves</au><au>Novaes, Rômulo Dias</au><au>Pereira, Gislaine Ribeiro</au><au>Galdino, Giovane</au><au>Carvalho, Flávia Chiva</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>163</volume><spage>105856</spage><epage>105856</epage><pages>105856-105856</pages><artnum>105856</artnum><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. 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| source | Access via ScienceDirect (Elsevier) |
| subjects | Chitooligosaccharide Chitosan Drug delivery system Hypromellose phthalate Methotrexate Polyelectrolyte complexes Rheumatoid arthritis |
| title | Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis |
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