Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain
The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague–Dawley rats. The effect o...
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| Veröffentlicht in: | Journal of controlled release 2016-02, Vol.224, p.69-76 |
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| creator | Manda, Prashanth Kushwaha, Avadhesh Singh Kundu, Santanu Shivakumar, H.N. Jo, Seong Bong Murthy, S. Narasimha |
| description | The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague–Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h−1. The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h−1 and 0.42±0.10h−1 respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain.
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| doi_str_mv | 10.1016/j.jconrel.2015.12.044 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2015.12.044</identifier><identifier>PMID: 26732557</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Administration, Intranasal ; Administration, Intravenous ; Analgesics - administration & dosage ; Analgesics - cerebrospinal fluid ; Analgesics - therapeutic use ; Animals ; Biological Availability ; Cerebrospinal fluid ; Chronic Pain - drug therapy ; Drug Delivery Systems ; Gels ; In situ gels ; Injections, Spinal ; Intranasal ; Male ; Olfactory Mucosa - metabolism ; omega-Conotoxins - administration & dosage ; omega-Conotoxins - cerebrospinal fluid ; omega-Conotoxins - therapeutic use ; Pharmaceutical Solutions ; Rats ; Rats, Sprague-Dawley ; Viscosity ; Ziconotide</subject><ispartof>Journal of controlled release, 2016-02, Vol.224, p.69-76</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-3ec46153ce8e4593c5e4df94d89b5d9262f309ade76b5ae53dd223a0b9eddc353</citedby><cites>FETCH-LOGICAL-c603t-3ec46153ce8e4593c5e4df94d89b5d9262f309ade76b5ae53dd223a0b9eddc353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2015.12.044$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26732557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manda, Prashanth</creatorcontrib><creatorcontrib>Kushwaha, Avadhesh Singh</creatorcontrib><creatorcontrib>Kundu, Santanu</creatorcontrib><creatorcontrib>Shivakumar, H.N.</creatorcontrib><creatorcontrib>Jo, Seong Bong</creatorcontrib><creatorcontrib>Murthy, S. Narasimha</creatorcontrib><title>Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague–Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h−1. The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h−1 and 0.42±0.10h−1 respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain.
[Display omitted]</description><subject>Administration, Intranasal</subject><subject>Administration, Intravenous</subject><subject>Analgesics - administration & dosage</subject><subject>Analgesics - cerebrospinal fluid</subject><subject>Analgesics - therapeutic use</subject><subject>Animals</subject><subject>Biological Availability</subject><subject>Cerebrospinal fluid</subject><subject>Chronic Pain - drug therapy</subject><subject>Drug Delivery Systems</subject><subject>Gels</subject><subject>In situ gels</subject><subject>Injections, Spinal</subject><subject>Intranasal</subject><subject>Male</subject><subject>Olfactory Mucosa - metabolism</subject><subject>omega-Conotoxins - administration & dosage</subject><subject>omega-Conotoxins - cerebrospinal fluid</subject><subject>omega-Conotoxins - therapeutic use</subject><subject>Pharmaceutical Solutions</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Viscosity</subject><subject>Ziconotide</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkTuPEzEUhS0EYsPCTwC5pJnBz_G4AaHlKa1EA7Xlse8QRxM72E5Q-PU4JKyggsrS9XfOfRyEnlLSU0KHF5t-41LMsPSMUNlT1hMh7qEVHRXvhNbyPlo1buz4IPUVelTKhhAiuVAP0RUbFGdSqhWa38ASDpCPOM34R2iWqQYPuCbsIMOUU9mFaBc8L_vg8SFYHGLNNtrSijtb19_tEc8p47puqgy2biHWk5tb5xSDa1CIj9GD2S4Fnlzea_Tl3dvPNx-620_vP968vu3cQHjtODgxUMkdjCCk5k6C8LMWftST9JoNbOZEWw9qmKQFyb1njFsyafDeccmv0cuz724_bcE7OM26mF0OW5uPJtlg_v6JYW2-poMRSqjxl8Hzi0FO3_ZQqtmG4mBZbIS0L4YqTbQUio3_gQ6C83HkrKHyjLp2z5JhvpuIEnOK02zMJU5zitNQZlqcTffsz3XuVL_za8CrMwDtqIcA2RQXIDrwIYOrxqfwjxY_AWqhtww</recordid><startdate>20160228</startdate><enddate>20160228</enddate><creator>Manda, Prashanth</creator><creator>Kushwaha, Avadhesh Singh</creator><creator>Kundu, Santanu</creator><creator>Shivakumar, H.N.</creator><creator>Jo, Seong Bong</creator><creator>Murthy, S. Narasimha</creator><general>Elsevier B.V</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20160228</creationdate><title>Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain</title><author>Manda, Prashanth ; Kushwaha, Avadhesh Singh ; Kundu, Santanu ; Shivakumar, H.N. ; Jo, Seong Bong ; Murthy, S. Narasimha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-3ec46153ce8e4593c5e4df94d89b5d9262f309ade76b5ae53dd223a0b9eddc353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Intranasal</topic><topic>Administration, Intravenous</topic><topic>Analgesics - administration & dosage</topic><topic>Analgesics - cerebrospinal fluid</topic><topic>Analgesics - therapeutic use</topic><topic>Animals</topic><topic>Biological Availability</topic><topic>Cerebrospinal fluid</topic><topic>Chronic Pain - drug therapy</topic><topic>Drug Delivery Systems</topic><topic>Gels</topic><topic>In situ gels</topic><topic>Injections, Spinal</topic><topic>Intranasal</topic><topic>Male</topic><topic>Olfactory Mucosa - metabolism</topic><topic>omega-Conotoxins - administration & dosage</topic><topic>omega-Conotoxins - cerebrospinal fluid</topic><topic>omega-Conotoxins - therapeutic use</topic><topic>Pharmaceutical Solutions</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Viscosity</topic><topic>Ziconotide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manda, Prashanth</creatorcontrib><creatorcontrib>Kushwaha, Avadhesh Singh</creatorcontrib><creatorcontrib>Kundu, Santanu</creatorcontrib><creatorcontrib>Shivakumar, H.N.</creatorcontrib><creatorcontrib>Jo, Seong Bong</creatorcontrib><creatorcontrib>Murthy, S. 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Narasimha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2016-02-28</date><risdate>2016</risdate><volume>224</volume><spage>69</spage><epage>76</epage><pages>69-76</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague–Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h−1. The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h−1 and 0.42±0.10h−1 respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain.
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| identifier | ISSN: 0168-3659 |
| ispartof | Journal of controlled release, 2016-02, Vol.224, p.69-76 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Administration, Intranasal Administration, Intravenous Analgesics - administration & dosage Analgesics - cerebrospinal fluid Analgesics - therapeutic use Animals Biological Availability Cerebrospinal fluid Chronic Pain - drug therapy Drug Delivery Systems Gels In situ gels Injections, Spinal Intranasal Male Olfactory Mucosa - metabolism omega-Conotoxins - administration & dosage omega-Conotoxins - cerebrospinal fluid omega-Conotoxins - therapeutic use Pharmaceutical Solutions Rats Rats, Sprague-Dawley Viscosity Ziconotide |
| title | Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain |
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