The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

Naveen K Thakral1, Alok R Ray1,2, Daniel Bar-Shalom3, Andr&eacute; Huss Eriksson4, Dipak K Majumdar51Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India; 2Biomedical Engineering Unit, All India Institute of Medical Science, New Delhi, India; 3...

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Autores principales:	Thakral NK, Ray AR, Bar-Shalom D, Eriksson AH, Majumdar DK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/da96f314c4bc42b5a45e491ed15b0582
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spelling	oai:doaj.org-article:da96f314c4bc42b5a45e491ed15b05822021-12-02T07:14:15ZThe quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres1176-91141178-2013https://doaj.org/article/da96f314c4bc42b5a45e491ed15b05822011-05-01T00:00:00Zhttp://www.dovepress.com/the-quest-for-targeted-delivery-in-colon-cancer-mucoadhesive-valdecoxi-a7497https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Naveen K Thakral1, Alok R Ray1,2, Daniel Bar-Shalom3, Andr&eacute; Huss Eriksson4, Dipak K Majumdar51Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India; 2Biomedical Engineering Unit, All India Institute of Medical Science, New Delhi, India; 3Department of Pharmaceutics and Analytical Chemistry, 4Bioneer:FARMA, Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, Pushp Vihar, New Delhi, IndiaAbstract: The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib.Keywords: Caco-2 cells, colon-delivery, COX-2 inhibitors, mucoadhesion, sodium alginateThakral NKRay ARBar-Shalom DEriksson AHMajumdar DKDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1057-1068 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Thakral NK Ray AR Bar-Shalom D Eriksson AH Majumdar DK The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
description	Naveen K Thakral1, Alok R Ray1,2, Daniel Bar-Shalom3, Andr&eacute; Huss Eriksson4, Dipak K Majumdar51Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India; 2Biomedical Engineering Unit, All India Institute of Medical Science, New Delhi, India; 3Department of Pharmaceutics and Analytical Chemistry, 4Bioneer:FARMA, Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, Pushp Vihar, New Delhi, IndiaAbstract: The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib.Keywords: Caco-2 cells, colon-delivery, COX-2 inhibitors, mucoadhesion, sodium alginate
format	article
author	Thakral NK Ray AR Bar-Shalom D Eriksson AH Majumdar DK
author_facet	Thakral NK Ray AR Bar-Shalom D Eriksson AH Majumdar DK
author_sort	Thakral NK
title	The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
title_short	The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
title_full	The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
title_fullStr	The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
title_full_unstemmed	The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
title_sort	quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/da96f314c4bc42b5a45e491ed15b0582
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The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

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