Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

K Lekha Nair1, Sankar Jagadeeshan2, S Asha Nair2, GS Vinod Kumar11Chemical Biology, Molecular Medicine Division, 2Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, IndiaAbstract: Nanoscaled devices have great potential for drug delivery applications due...

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Autores principales:	Lekha Nair K, Jagadeeshan S, Nair SA, Kumar GSV
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/27cc020fb252455cbb7814a5be662a1b
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spelling	oai:doaj.org-article:27cc020fb252455cbb7814a5be662a1b2021-12-02T11:20:50ZBiological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA1176-91141178-2013https://doaj.org/article/27cc020fb252455cbb7814a5be662a1b2011-08-01T00:00:00Zhttp://www.dovepress.com/biological-evaluation-of-5-fluorouracil-nanoparticles-for-cancer-chemo-a8093https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013K Lekha Nair1, Sankar Jagadeeshan2, S Asha Nair2, GS Vinod Kumar11Chemical Biology, Molecular Medicine Division, 2Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, IndiaAbstract: Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.Keywords: 5-FU, poly (D, L-lactic-co-glycolic acid), controlled releaseLekha Nair KJagadeeshan SNair SAKumar GSVDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1685-1697 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lekha Nair K Jagadeeshan S Nair SA Kumar GSV Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
description	K Lekha Nair1, Sankar Jagadeeshan2, S Asha Nair2, GS Vinod Kumar11Chemical Biology, Molecular Medicine Division, 2Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, IndiaAbstract: Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.Keywords: 5-FU, poly (D, L-lactic-co-glycolic acid), controlled release
format	article
author	Lekha Nair K Jagadeeshan S Nair SA Kumar GSV
author_facet	Lekha Nair K Jagadeeshan S Nair SA Kumar GSV
author_sort	Lekha Nair K
title	Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
title_short	Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
title_full	Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
title_fullStr	Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
title_full_unstemmed	Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA
title_sort	biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, plga
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/27cc020fb252455cbb7814a5be662a1b
work_keys_str_mv	AT lekhanairk biologicalevaluationof5fluorouracilnanoparticlesforcancerchemotherapyanditsdependenceonthecarrierplga AT jagadeeshans biologicalevaluationof5fluorouracilnanoparticlesforcancerchemotherapyanditsdependenceonthecarrierplga AT nairsa biologicalevaluationof5fluorouracilnanoparticlesforcancerchemotherapyanditsdependenceonthecarrierplga AT kumargsv biologicalevaluationof5fluorouracilnanoparticlesforcancerchemotherapyanditsdependenceonthecarrierplga
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Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

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