In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer
Objectives Colorectal cancer (CRC) is a life‐threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti‐inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. Th...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2015-05, Vol.67 (5), p.685-695 |
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| creator | McDonald, Bernard F. Quinn, Alison M. Devers, Tomas Cullen, Alan Coulter, Ivan S. Marison, Ian W. Loughran, Sinéad T. |
| description | Objectives
Colorectal cancer (CRC) is a life‐threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti‐inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX.
Methods
The study involved the assessment of the effectiveness of CLX formulations in an in‐vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in‐vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in‐vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled‐up using vibrating‐jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release.
Key findings
In‐vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon‐targeted CLX microbeads suitable for use in a future in‐vivo mouse study.
Conclusions
These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardi |
| doi_str_mv | 10.1111/jphp.12372 |
| format | Article |
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Colorectal cancer (CRC) is a life‐threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti‐inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX.
Methods
The study involved the assessment of the effectiveness of CLX formulations in an in‐vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in‐vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in‐vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled‐up using vibrating‐jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release.
Key findings
In‐vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon‐targeted CLX microbeads suitable for use in a future in‐vivo mouse study.
Conclusions
These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/jphp.12372</identifier><identifier>PMID: 25650335</identifier><identifier>CODEN: JPPMAB</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Celecoxib - administration & dosage ; Celecoxib - adverse effects ; Celecoxib - chemistry ; Celecoxib - therapeutic use ; Cell Movement - drug effects ; Cell Survival - drug effects ; Chemistry, Pharmaceutical - methods ; Colorectal cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - prevention & control ; drug delivery ; Drug Delivery Systems - methods ; Drug Liberation ; formulation ; HT29 ; HT29 Cells ; Humans ; Medical research ; Microspheres ; Motility ; Rodents ; Solubility</subject><ispartof>Journal of pharmacy and pharmacology, 2015-05, Vol.67 (5), p.685-695</ispartof><rights>2015 Royal Pharmaceutical Society</rights><rights>2015 Royal Pharmaceutical Society.</rights><rights>Copyright © 2015 Royal Pharmaceutical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4652-1add9d9c805fda1cd7fe8c10b6d54061d4c34ba2e43bdec805b72a310a5440b43</citedby><cites>FETCH-LOGICAL-c4652-1add9d9c805fda1cd7fe8c10b6d54061d4c34ba2e43bdec805b72a310a5440b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjphp.12372$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjphp.12372$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25650335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McDonald, Bernard F.</creatorcontrib><creatorcontrib>Quinn, Alison M.</creatorcontrib><creatorcontrib>Devers, Tomas</creatorcontrib><creatorcontrib>Cullen, Alan</creatorcontrib><creatorcontrib>Coulter, Ivan S.</creatorcontrib><creatorcontrib>Marison, Ian W.</creatorcontrib><creatorcontrib>Loughran, Sinéad T.</creatorcontrib><title>In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>Objectives
Colorectal cancer (CRC) is a life‐threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti‐inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX.
Methods
The study involved the assessment of the effectiveness of CLX formulations in an in‐vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in‐vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in‐vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled‐up using vibrating‐jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release.
Key findings
In‐vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon‐targeted CLX microbeads suitable for use in a future in‐vivo mouse study.
Conclusions
These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.</description><subject>Celecoxib - administration & dosage</subject><subject>Celecoxib - adverse effects</subject><subject>Celecoxib - chemistry</subject><subject>Celecoxib - therapeutic use</subject><subject>Cell Movement - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - prevention & control</subject><subject>drug delivery</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Liberation</subject><subject>formulation</subject><subject>HT29</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Medical research</subject><subject>Microspheres</subject><subject>Motility</subject><subject>Rodents</subject><subject>Solubility</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0Eokvhwg9AlrggpBR_Z_eIVrBbVMEeQPRmOfZEmyWJg-0sbX99HbLtgQNz8RyeeTSeF6HXlFzQXB8Ow364oIyX7AlaMCJYUVK5fIoWhDBWcFnyM_QixgMhpFRKPUdnTCpJOJcLdHfZF8cmBY_t3gRjE4QmmtT4HvsaG9z7I7TYQgvW3zQV7hobfAXG4dqHbmxnNPc47QGnACZ10CdseoeHAMfcn1zWtz6ATSbrTG8hvETPatNGeHV6z9GPz5--r7fF1bfN5frjVWGFkqygxrmVW9klkbUz1LqyhqWlpFJOCqKoE5aLyjAQvHIwYVXJDKfESCFIJfg5ejd7h-B_jxCT7pqYf9SaHvwYNVWlpGrFOM3o23_Qgx9Dn7ebKJGvJthEvZ-pfIoYA9R6CE1nwq2mRE-J6CkR_TeRDL85KceqA_eIPkSQAToDf5oWbv-j0l92292DtJhnmpjg5nHGhF9albyU-ufXjb5eb-iObJW-5vc6yacw</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>McDonald, Bernard F.</creator><creator>Quinn, Alison M.</creator><creator>Devers, Tomas</creator><creator>Cullen, Alan</creator><creator>Coulter, Ivan S.</creator><creator>Marison, Ian W.</creator><creator>Loughran, Sinéad T.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>201505</creationdate><title>In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer</title><author>McDonald, Bernard F. ; Quinn, Alison M. ; Devers, Tomas ; Cullen, Alan ; Coulter, Ivan S. ; Marison, Ian W. ; Loughran, Sinéad T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4652-1add9d9c805fda1cd7fe8c10b6d54061d4c34ba2e43bdec805b72a310a5440b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Celecoxib - administration & dosage</topic><topic>Celecoxib - adverse effects</topic><topic>Celecoxib - chemistry</topic><topic>Celecoxib - therapeutic use</topic><topic>Cell Movement - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - prevention & control</topic><topic>drug delivery</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Liberation</topic><topic>formulation</topic><topic>HT29</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Medical research</topic><topic>Microspheres</topic><topic>Motility</topic><topic>Rodents</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McDonald, Bernard F.</creatorcontrib><creatorcontrib>Quinn, Alison M.</creatorcontrib><creatorcontrib>Devers, Tomas</creatorcontrib><creatorcontrib>Cullen, Alan</creatorcontrib><creatorcontrib>Coulter, Ivan S.</creatorcontrib><creatorcontrib>Marison, Ian W.</creatorcontrib><creatorcontrib>Loughran, Sinéad T.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McDonald, Bernard F.</au><au>Quinn, Alison M.</au><au>Devers, Tomas</au><au>Cullen, Alan</au><au>Coulter, Ivan S.</au><au>Marison, Ian W.</au><au>Loughran, Sinéad T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2015-05</date><risdate>2015</risdate><volume>67</volume><issue>5</issue><spage>685</spage><epage>695</epage><pages>685-695</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><coden>JPPMAB</coden><abstract>Objectives
Colorectal cancer (CRC) is a life‐threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti‐inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX.
Methods
The study involved the assessment of the effectiveness of CLX formulations in an in‐vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in‐vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in‐vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled‐up using vibrating‐jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release.
Key findings
In‐vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon‐targeted CLX microbeads suitable for use in a future in‐vivo mouse study.
Conclusions
These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25650335</pmid><doi>10.1111/jphp.12372</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of pharmacy and pharmacology, 2015-05, Vol.67 (5), p.685-695 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Celecoxib - administration & dosage Celecoxib - adverse effects Celecoxib - chemistry Celecoxib - therapeutic use Cell Movement - drug effects Cell Survival - drug effects Chemistry, Pharmaceutical - methods Colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - prevention & control drug delivery Drug Delivery Systems - methods Drug Liberation formulation HT29 HT29 Cells Humans Medical research Microspheres Motility Rodents Solubility |
| title | In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer |
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