Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles
Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7's role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for pot...
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| Veröffentlicht in: | International journal of molecular sciences 2021-03, Vol.22 (6), p.3206 |
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| creator | Nozal, Vanesa Rojas-Prats, Elisa Maestro, Inés Gil, Carmen Perez, Daniel I Martinez, Ana |
| description | Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7's role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(
)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor. |
| doi_str_mv | 10.3390/ijms22063206 |
| format | Article |
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)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.</description><identifier>ISSN: 1422-0067</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22063206</identifier><identifier>PMID: 33809846</identifier><language>eng</language><publisher>Switzerland: MDPI</publisher><subject>Animals ; Brain - drug effects ; Brain - metabolism ; Cell Survival - drug effects ; Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors ; Delayed-Action Preparations - chemistry ; Drug Carriers - chemistry ; Drug Compounding ; Drug Liberation ; Humans ; Mice ; Molecular Structure ; Nanoparticles - chemistry ; Nanoparticles - ultrastructure ; Particle Size ; Permeability ; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry ; Quinazolinones - chemistry ; Quinazolinones - pharmacokinetics</subject><ispartof>International journal of molecular sciences, 2021-03, Vol.22 (6), p.3206</ispartof><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-814936bab4564d401af135f469cd8e11e44f00bbe9654a2872c326a69bedd2dd3</citedby><cites>FETCH-LOGICAL-c384t-814936bab4564d401af135f469cd8e11e44f00bbe9654a2872c326a69bedd2dd3</cites><orcidid>0000-0001-5260-5683 ; 0000-0002-5747-8764 ; 0000-0002-3882-6081 ; 0000-0002-2707-8110</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004175/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004175/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33809846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nozal, Vanesa</creatorcontrib><creatorcontrib>Rojas-Prats, Elisa</creatorcontrib><creatorcontrib>Maestro, Inés</creatorcontrib><creatorcontrib>Gil, Carmen</creatorcontrib><creatorcontrib>Perez, Daniel I</creatorcontrib><creatorcontrib>Martinez, Ana</creatorcontrib><title>Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7's role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(
)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.</description><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors</subject><subject>Delayed-Action Preparations - chemistry</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Compounding</subject><subject>Drug Liberation</subject><subject>Humans</subject><subject>Mice</subject><subject>Molecular Structure</subject><subject>Nanoparticles - chemistry</subject><subject>Nanoparticles - ultrastructure</subject><subject>Particle Size</subject><subject>Permeability</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</subject><subject>Quinazolinones - chemistry</subject><subject>Quinazolinones - pharmacokinetics</subject><issn>1422-0067</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUE1LAzEQDaLYWr15lvwAV_O16e5FqEVroWpRe16ym9k2JZuUZFvw37tSlXoY5g3z5j3mIXRJyQ3nObk16yYyRiTv6gj1qWAsIUQOjw9wD53FuCaEcZbmp6jHeUbyTMg-0tNmE_wONB571wZvbQffwIKKgJXT-D4o4_AcHLRBtcY77GvcrgC_N8pa_OwtVFvbjVTgRTRuieezyQi_KOc3KrSmshDP0UmtbISLnz5Ai8eHj_FTMnudTMejWVLxTLRJRkXOZalKkUqhBaGqpjythcwrnQGlIERNSFlCLlOhWDZkFWdSybwErZnWfIDu9rqbbdmArqD7SNliE0yjwmfhlSn-b5xZFUu_KzJCBB2mncD1XqAKPsYA9d8tJcV32sVh2h396tDvj_wbL_8Cu_J8hA</recordid><startdate>20210322</startdate><enddate>20210322</enddate><creator>Nozal, Vanesa</creator><creator>Rojas-Prats, Elisa</creator><creator>Maestro, Inés</creator><creator>Gil, Carmen</creator><creator>Perez, Daniel I</creator><creator>Martinez, Ana</creator><general>MDPI</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>5PM</scope><orcidid>https://orcid.org/0000-0001-5260-5683</orcidid><orcidid>https://orcid.org/0000-0002-5747-8764</orcidid><orcidid>https://orcid.org/0000-0002-3882-6081</orcidid><orcidid>https://orcid.org/0000-0002-2707-8110</orcidid></search><sort><creationdate>20210322</creationdate><title>Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles</title><author>Nozal, Vanesa ; 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)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.</abstract><cop>Switzerland</cop><pub>MDPI</pub><pmid>33809846</pmid><doi>10.3390/ijms22063206</doi><orcidid>https://orcid.org/0000-0001-5260-5683</orcidid><orcidid>https://orcid.org/0000-0002-5747-8764</orcidid><orcidid>https://orcid.org/0000-0002-3882-6081</orcidid><orcidid>https://orcid.org/0000-0002-2707-8110</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Brain - drug effects Brain - metabolism Cell Survival - drug effects Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors Delayed-Action Preparations - chemistry Drug Carriers - chemistry Drug Compounding Drug Liberation Humans Mice Molecular Structure Nanoparticles - chemistry Nanoparticles - ultrastructure Particle Size Permeability Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Quinazolinones - chemistry Quinazolinones - pharmacokinetics |
| title | Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles |
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