Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient
The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous soluti...
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| Veröffentlicht in: | AAPS PharmSciTech 2005-10, Vol.6 (3), p.E536 |
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| creator | Asthana, Abhay Chauhan, Abhay Singh Diwan, Prakash Vamanrao Jain, Narendra Kumar |
| description | The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation. |
| doi_str_mv | 10.1208/pt060367 |
| format | Article |
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Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation.</description><identifier>EISSN: 1530-9932</identifier><identifier>DOI: 10.1208/pt060367</identifier><identifier>PMID: 16354015</identifier><language>eng</language><publisher>United States</publisher><subject>Acids - administration & dosage ; Acids - pharmacokinetics ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics ; Delayed-Action Preparations - administration & dosage ; Delayed-Action Preparations - pharmacokinetics ; Dendrimers ; Drug Delivery Systems - methods ; Male ; Nanostructures ; Polyamines - administration & dosage ; Polyamines - pharmacokinetics ; Rats ; Rats, Sprague-Dawley</subject><ispartof>AAPS PharmSciTech, 2005-10, Vol.6 (3), p.E536</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16354015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asthana, Abhay</creatorcontrib><creatorcontrib>Chauhan, Abhay Singh</creatorcontrib><creatorcontrib>Diwan, Prakash Vamanrao</creatorcontrib><creatorcontrib>Jain, Narendra Kumar</creatorcontrib><title>Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient</title><title>AAPS PharmSciTech</title><addtitle>AAPS PharmSciTech</addtitle><description>The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation.</description><subject>Acids - administration & dosage</subject><subject>Acids - pharmacokinetics</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</subject><subject>Delayed-Action Preparations - administration & dosage</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Dendrimers</subject><subject>Drug Delivery Systems - methods</subject><subject>Male</subject><subject>Nanostructures</subject><subject>Polyamines - administration & dosage</subject><subject>Polyamines - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>1530-9932</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEtLAzEcxIMgtlbBTyA51sNqHpuNOZbiC1rsQc8lj38kspssSSr0A_i9XVAvMzDzYw6D0BUlt5SR-7uxko7wTp6gORWcNEpxNkPnpXwSwjhV_AzNaMdFS6iYo-9d6o9LPQSXJolwg5e71Xa1vcEOosuhBoujjqnUfLD1kKFgnzK2Kdac-h4cLqFCU0awwU-sgz58QT7i5LG2wU2RjjU0IfpeD4Ouaeq0rROEQ_zI4ALEeoFOve4LXP75Ar0_Prytn5vN69PLerVpRiZVbYy0TiorDDXKSuu9AiaJAd1ZENJ0irTAnKBCCm0p86btqHJaQ-usUNzyBbr-3R0PZgC3H3MYdD7u___gP-ojYxM</recordid><startdate>20051027</startdate><enddate>20051027</enddate><creator>Asthana, Abhay</creator><creator>Chauhan, Abhay Singh</creator><creator>Diwan, Prakash Vamanrao</creator><creator>Jain, Narendra Kumar</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20051027</creationdate><title>Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient</title><author>Asthana, Abhay ; Chauhan, Abhay Singh ; Diwan, Prakash Vamanrao ; Jain, Narendra Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p279t-b7cd79c5b1b9c7cff9e270bea6ce57b6904e2d51575ac12fb4619daae4dc593c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acids - administration & dosage</topic><topic>Acids - pharmacokinetics</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</topic><topic>Delayed-Action Preparations - administration & dosage</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Dendrimers</topic><topic>Drug Delivery Systems - methods</topic><topic>Male</topic><topic>Nanostructures</topic><topic>Polyamines - administration & dosage</topic><topic>Polyamines - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asthana, Abhay</creatorcontrib><creatorcontrib>Chauhan, Abhay Singh</creatorcontrib><creatorcontrib>Diwan, Prakash Vamanrao</creatorcontrib><creatorcontrib>Jain, Narendra Kumar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>AAPS PharmSciTech</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asthana, Abhay</au><au>Chauhan, Abhay Singh</au><au>Diwan, Prakash Vamanrao</au><au>Jain, Narendra Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient</atitle><jtitle>AAPS PharmSciTech</jtitle><addtitle>AAPS PharmSciTech</addtitle><date>2005-10-27</date><risdate>2005</risdate><volume>6</volume><issue>3</issue><spage>E536</spage><pages>E536-</pages><eissn>1530-9932</eissn><abstract>The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation.</abstract><cop>United States</cop><pmid>16354015</pmid><doi>10.1208/pt060367</doi><oa>free_for_read</oa></addata></record> |
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| identifier | EISSN: 1530-9932 |
| ispartof | AAPS PharmSciTech, 2005-10, Vol.6 (3), p.E536 |
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| source | MEDLINE; SpringerNature Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids - administration & dosage Acids - pharmacokinetics Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics Delayed-Action Preparations - administration & dosage Delayed-Action Preparations - pharmacokinetics Dendrimers Drug Delivery Systems - methods Male Nanostructures Polyamines - administration & dosage Polyamines - pharmacokinetics Rats Rats, Sprague-Dawley |
| title | Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient |
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