Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats
Formulation of antibiotics as inhalable products is proposed to improve their therapeutic index when intended for the treatment of pulmonary infections; as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional admi...
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| Veröffentlicht in: | Journal of antibiotics 2013-08, Vol.66 (8), p.447-451 |
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| creator | de Jesús Valle, M J González, J Garavís López, F González Navarro, A Sánchez |
| description | Formulation of antibiotics as inhalable products is proposed to improve their therapeutic index when intended for the treatment of pulmonary infections; as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional administration routes. An experimental study has been performed to compare the pulmonary disposition of vancomycin after inhalation of the drug formulated as a solution and as lipid vesicles (conventional liposomes or liposomes modified with chitosan). Vancomycin concentrations were determined in bronchoalveolar fluid, pulmonary tissue and blood samples from 27 Wistar rats distributed in three groups subjected to nebulisation of the drug formulated as a solution, conventional liposomes or chitosomes. Statistically significant differences between the mean drug concentrations in bronchoalveolar lavage (BALF) and lung tissue were found upon comparing the solution to lipid vesicles (116.95 μg ml
−1
±62.13 versus 68.34 μg ml
−1
±28.90 for liposomes and 65.36±22.11 μg g
−1
for chitosomes in BALF; 222.74±37.15 μg g
−1
versus 357.17±65.37 μg g
−1
for liposomes and 378.83±85.87 μg g
−1
for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation. |
| doi_str_mv | 10.1038/ja.2013.32 |
| format | Article |
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−1
±62.13 versus 68.34 μg ml
−1
±28.90 for liposomes and 65.36±22.11 μg g
−1
for chitosomes in BALF; 222.74±37.15 μg g
−1
versus 357.17±65.37 μg g
−1
for liposomes and 378.83±85.87 μg g
−1
for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/ja.2013.32</identifier><identifier>PMID: 23677032</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/326/22/1290 ; 692/699/1785 ; 692/700/565/1436 ; Administration, Inhalation ; Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibiotics ; Bacteriology ; Biological Transport ; Biomedical and Life Sciences ; Bioorganic Chemistry ; Bronchoalveolar Lavage Fluid - chemistry ; Chitosan - chemistry ; Drug Delivery Systems ; Inhalation ; Life Sciences ; Liposomes ; Lung - metabolism ; Male ; Medicinal Chemistry ; Microbiology ; Nebulizers and Vaporizers ; Organic Chemistry ; original-article ; Rats ; Rats, Wistar ; Tissue Distribution ; Tissues ; Vancomycin - administration & dosage ; Vancomycin - pharmacokinetics</subject><ispartof>Journal of antibiotics, 2013-08, Vol.66 (8), p.447-451</ispartof><rights>Japan Antibiotics Research Association 2013</rights><rights>Copyright Nature Publishing Group Aug 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-308c4bf5ee4e8ce4bdf7e92832f7c471b1abfc6f5ffb5bf891ddf6761578c2c63</citedby><cites>FETCH-LOGICAL-c506t-308c4bf5ee4e8ce4bdf7e92832f7c471b1abfc6f5ffb5bf891ddf6761578c2c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23677032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Jesús Valle, M J</creatorcontrib><creatorcontrib>González, J Garavís</creatorcontrib><creatorcontrib>López, F González</creatorcontrib><creatorcontrib>Navarro, A Sánchez</creatorcontrib><title>Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>Formulation of antibiotics as inhalable products is proposed to improve their therapeutic index when intended for the treatment of pulmonary infections; as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional administration routes. An experimental study has been performed to compare the pulmonary disposition of vancomycin after inhalation of the drug formulated as a solution and as lipid vesicles (conventional liposomes or liposomes modified with chitosan). Vancomycin concentrations were determined in bronchoalveolar fluid, pulmonary tissue and blood samples from 27 Wistar rats distributed in three groups subjected to nebulisation of the drug formulated as a solution, conventional liposomes or chitosomes. Statistically significant differences between the mean drug concentrations in bronchoalveolar lavage (BALF) and lung tissue were found upon comparing the solution to lipid vesicles (116.95 μg ml
−1
±62.13 versus 68.34 μg ml
−1
±28.90 for liposomes and 65.36±22.11 μg g
−1
for chitosomes in BALF; 222.74±37.15 μg g
−1
versus 357.17±65.37 μg g
−1
for liposomes and 378.83±85.87 μg g
−1
for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation.</description><subject>631/326/22/1290</subject><subject>692/699/1785</subject><subject>692/700/565/1436</subject><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Antibiotics</subject><subject>Bacteriology</subject><subject>Biological Transport</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Chitosan - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Inhalation</subject><subject>Life Sciences</subject><subject>Liposomes</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Medicinal Chemistry</subject><subject>Microbiology</subject><subject>Nebulizers and Vaporizers</subject><subject>Organic Chemistry</subject><subject>original-article</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Tissue Distribution</subject><subject>Tissues</subject><subject>Vancomycin - administration & dosage</subject><subject>Vancomycin - pharmacokinetics</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpl0E9LwzAYBvAgipvTix9AAl5E6cy_NulRhk5hoAc9hzRNJKVtatIO5qe3Y1NET-_h_fG8Lw8A5xjNMaLitlJzgjCdU3IAplgInGCW5YdgihDBiRAETcBJjBVClFMujsGE0IxzRMkULF-GuvGtChtYutj56HrnW-gtXKtW-2ajXQtbUwy1-zQlVBHWrnMlXJvodG0iHNdB9fEUHFlVR3O2nzPw9nD_unhMVs_Lp8XdKtEpyvqEIqFZYVNjmBHasKK03OREUGK5ZhwXWBVWZza1tkgLK3JcljbjGU650ERndAaudrld8B-Dib1sXNSmrlVr_BAlZkSkmIkMjfTyD638ENrxO4m54CmjOWKjut4pHXyMwVjZBdeMfUiM5LZeWSm5rVdSMuKLfeRQNKb8od99juBmB-K4at9N-HXzf9wXl1eDzw</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>de Jesús Valle, M J</creator><creator>González, J Garavís</creator><creator>López, F González</creator><creator>Navarro, A Sánchez</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20130801</creationdate><title>Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats</title><author>de Jesús Valle, M J ; 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as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional administration routes. An experimental study has been performed to compare the pulmonary disposition of vancomycin after inhalation of the drug formulated as a solution and as lipid vesicles (conventional liposomes or liposomes modified with chitosan). Vancomycin concentrations were determined in bronchoalveolar fluid, pulmonary tissue and blood samples from 27 Wistar rats distributed in three groups subjected to nebulisation of the drug formulated as a solution, conventional liposomes or chitosomes. Statistically significant differences between the mean drug concentrations in bronchoalveolar lavage (BALF) and lung tissue were found upon comparing the solution to lipid vesicles (116.95 μg ml
−1
±62.13 versus 68.34 μg ml
−1
±28.90 for liposomes and 65.36±22.11 μg g
−1
for chitosomes in BALF; 222.74±37.15 μg g
−1
versus 357.17±65.37 μg g
−1
for liposomes and 378.83±85.87 μg g
−1
for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23677032</pmid><doi>10.1038/ja.2013.32</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antibiotics, 2013-08, Vol.66 (8), p.447-451 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 631/326/22/1290 692/699/1785 692/700/565/1436 Administration, Inhalation Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Bacteriology Biological Transport Biomedical and Life Sciences Bioorganic Chemistry Bronchoalveolar Lavage Fluid - chemistry Chitosan - chemistry Drug Delivery Systems Inhalation Life Sciences Liposomes Lung - metabolism Male Medicinal Chemistry Microbiology Nebulizers and Vaporizers Organic Chemistry original-article Rats Rats, Wistar Tissue Distribution Tissues Vancomycin - administration & dosage Vancomycin - pharmacokinetics |
| title | Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats |
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