Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits
Ocular bioavailability of acyclovir (ACV) was increased by chemically linking ACV to squalene, obtaining 4′- trisnorsqualenoylacyclovir (SQACV), which spontaneously forms nanoassemblies. The graph shows tear fluid concentration vs time profiles of ACV after the administration of SQACV and ACV formul...
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| Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2012, Vol.80 (1), p.39-45 |
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| container_title | European journal of pharmaceutics and biopharmaceutics |
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| creator | Stella, Barbara Arpicco, Silvia Rocco, Flavio Burgalassi, Susi Nicosia, Nadia Tampucci, Silvia Chetoni, Patrizia Cattel, Luigi |
| description | Ocular bioavailability of acyclovir (ACV) was increased by chemically linking ACV to squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), which spontaneously forms nanoassemblies. The graph shows tear fluid concentration
vs time profiles of ACV after the administration of SQACV and ACV formulations.
The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4′-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug.
Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug. |
| doi_str_mv | 10.1016/j.ejpb.2011.10.001 |
| format | Article |
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trisnorsqualenoylacyclovir (SQACV), which spontaneously forms nanoassemblies. The graph shows tear fluid concentration
vs time profiles of ACV after the administration of SQACV and ACV formulations.
The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4′-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug.
Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2011.10.001</identifier><identifier>PMID: 22008147</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Acyclovir ; Acyclovir - administration & dosage ; Acyclovir - chemistry ; Acyclovir - pharmacokinetics ; Administration, Ophthalmic ; Animals ; Antiviral Agents - administration & dosage ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacokinetics ; Aqueous Humor - drug effects ; Aqueous Humor - metabolism ; Biological and medical sciences ; Biological Availability ; Chemistry, Pharmaceutical - methods ; Drug Stability ; General pharmacology ; Male ; Medical sciences ; Nanoassemblies ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Nanotechnology - methods ; Ocular pharmacokinetic ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Prodrugs - administration & dosage ; Prodrugs - chemistry ; Prodrugs - pharmacokinetics ; Rabbits ; Solubility ; Squalene ; Squalene - chemistry ; Tears - drug effects ; Tears - metabolism</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2012, Vol.80 (1), p.39-45</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-119f62b039d966d27ba37ccd788035b1be50ecb8918f2299be2a61bfdbf93ec43</citedby><cites>FETCH-LOGICAL-c429t-119f62b039d966d27ba37ccd788035b1be50ecb8918f2299be2a61bfdbf93ec43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejpb.2011.10.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25400020$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22008147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stella, Barbara</creatorcontrib><creatorcontrib>Arpicco, Silvia</creatorcontrib><creatorcontrib>Rocco, Flavio</creatorcontrib><creatorcontrib>Burgalassi, Susi</creatorcontrib><creatorcontrib>Nicosia, Nadia</creatorcontrib><creatorcontrib>Tampucci, Silvia</creatorcontrib><creatorcontrib>Chetoni, Patrizia</creatorcontrib><creatorcontrib>Cattel, Luigi</creatorcontrib><title>Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>Eur J Pharm Biopharm</addtitle><description>Ocular bioavailability of acyclovir (ACV) was increased by chemically linking ACV to squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), which spontaneously forms nanoassemblies. The graph shows tear fluid concentration
vs time profiles of ACV after the administration of SQACV and ACV formulations.
The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4′-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug.
Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug.</description><subject>Acyclovir</subject><subject>Acyclovir - administration & dosage</subject><subject>Acyclovir - chemistry</subject><subject>Acyclovir - pharmacokinetics</subject><subject>Administration, Ophthalmic</subject><subject>Animals</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacokinetics</subject><subject>Aqueous Humor - drug effects</subject><subject>Aqueous Humor - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Drug Stability</subject><subject>General pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nanoassemblies</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Nanotechnology - methods</subject><subject>Ocular pharmacokinetic</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - pharmacokinetics</subject><subject>Rabbits</subject><subject>Solubility</subject><subject>Squalene</subject><subject>Squalene - chemistry</subject><subject>Tears - drug effects</subject><subject>Tears - metabolism</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuEzEQhi0EoqHwAhzQXhCnTT22s7tGXKoKSqWK9gBny_aOhYPXDvZupLw9jhLojdNIv775NfqGkLdA10Chu9qucbsza0YBarCmFJ6RFQw9b7kQ8JysqOSy7QTABXlVypZSKvrN8JJcMEbpAKJfEf8txV0Khwmzt03UMelScDLBY2lcyk2yS9C50ePkoy9z1rNPsUmu0fZgQ9r7_LF5_KnzpG365SPOtQb3Oiwn0Mcma2P8XF6TF06Hgm_O85L8-PL5-83X9v7h9u7m-r61gsm5BZCuY4ZyOcquG1lvNO-tHfthoHxjwOCGojWDhMExJqVBpjswbjROcrSCX5IPp95dTr8XLLOafLEYgo6YlqIkMMEG4F0l2Ym0OZWS0ald9pPOBwVUHQ2rrToaVkfDx6warkvvzvWLmXD8t_JXaQXenwFdrA4u62h9eeI2ov6B0cp9OnFYZew9ZlWsx2hx9BntrMbk_3fHHx5gm_0</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Stella, Barbara</creator><creator>Arpicco, Silvia</creator><creator>Rocco, Flavio</creator><creator>Burgalassi, Susi</creator><creator>Nicosia, Nadia</creator><creator>Tampucci, Silvia</creator><creator>Chetoni, Patrizia</creator><creator>Cattel, Luigi</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>2012</creationdate><title>Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits</title><author>Stella, Barbara ; Arpicco, Silvia ; Rocco, Flavio ; Burgalassi, Susi ; Nicosia, Nadia ; Tampucci, Silvia ; Chetoni, Patrizia ; Cattel, Luigi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-119f62b039d966d27ba37ccd788035b1be50ecb8918f2299be2a61bfdbf93ec43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acyclovir</topic><topic>Acyclovir - administration & dosage</topic><topic>Acyclovir - chemistry</topic><topic>Acyclovir - pharmacokinetics</topic><topic>Administration, Ophthalmic</topic><topic>Animals</topic><topic>Antiviral Agents - administration & dosage</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacokinetics</topic><topic>Aqueous Humor - drug effects</topic><topic>Aqueous Humor - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Drug Stability</topic><topic>General pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nanoassemblies</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Nanotechnology - methods</topic><topic>Ocular pharmacokinetic</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Prodrugs - administration & dosage</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - pharmacokinetics</topic><topic>Rabbits</topic><topic>Solubility</topic><topic>Squalene</topic><topic>Squalene - chemistry</topic><topic>Tears - drug effects</topic><topic>Tears - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stella, Barbara</creatorcontrib><creatorcontrib>Arpicco, Silvia</creatorcontrib><creatorcontrib>Rocco, Flavio</creatorcontrib><creatorcontrib>Burgalassi, Susi</creatorcontrib><creatorcontrib>Nicosia, Nadia</creatorcontrib><creatorcontrib>Tampucci, Silvia</creatorcontrib><creatorcontrib>Chetoni, Patrizia</creatorcontrib><creatorcontrib>Cattel, Luigi</creatorcontrib><collection>Pascal-Francis</collection><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>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stella, Barbara</au><au>Arpicco, Silvia</au><au>Rocco, Flavio</au><au>Burgalassi, Susi</au><au>Nicosia, Nadia</au><au>Tampucci, Silvia</au><au>Chetoni, Patrizia</au><au>Cattel, Luigi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2012</date><risdate>2012</risdate><volume>80</volume><issue>1</issue><spage>39</spage><epage>45</epage><pages>39-45</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>Ocular bioavailability of acyclovir (ACV) was increased by chemically linking ACV to squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), which spontaneously forms nanoassemblies. The graph shows tear fluid concentration
vs time profiles of ACV after the administration of SQACV and ACV formulations.
The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4′-
trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4′-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug.
Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>22008147</pmid><doi>10.1016/j.ejpb.2011.10.001</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| subjects | Acyclovir Acyclovir - administration & dosage Acyclovir - chemistry Acyclovir - pharmacokinetics Administration, Ophthalmic Animals Antiviral Agents - administration & dosage Antiviral Agents - chemistry Antiviral Agents - pharmacokinetics Aqueous Humor - drug effects Aqueous Humor - metabolism Biological and medical sciences Biological Availability Chemistry, Pharmaceutical - methods Drug Stability General pharmacology Male Medical sciences Nanoassemblies Nanoparticles - administration & dosage Nanoparticles - chemistry Nanotechnology - methods Ocular pharmacokinetic Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Prodrugs - administration & dosage Prodrugs - chemistry Prodrugs - pharmacokinetics Rabbits Solubility Squalene Squalene - chemistry Tears - drug effects Tears - metabolism |
| title | Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits |
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