Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Bi...

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Autores principales:	Srivastava AK, Bhatnagar P, Singh M, Mishra S, Kumar P, Shukla Y, Gupta KC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6fefe448976343398e24f25f4a8a414e
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spelling	oai:doaj.org-article:6fefe448976343398e24f25f4a8a414e2021-12-02T07:15:35ZSynthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage1176-91141178-2013https://doaj.org/article/6fefe448976343398e24f25f4a8a414e2013-04-01T00:00:00Zhttp://www.dovepress.com/synthesis-of-plga-nanoparticles-of-tea-polyphenols-and-their-strong-in-a12766https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, India Abstract: In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF]) and green (epigallocatechin-3-gallate [EGCG]) tea in poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA)-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically) of mouse skin with either TF or EGCG (100 µg/mouse) doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk), 57.63% (1/10th of bulk), and 63.14% (1/5th of bulk) prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3) and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2) as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior ability to prevent DMBA-induced DNA damage at much lower concentrations, thus opening a new dimension in chemoprevention research. Keywords: DNA alkaline unwinding assay, mouse skin, DNA repairSrivastava AKBhatnagar PSingh MMishra SKumar PShukla YGupta KCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1451-1462 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Srivastava AK Bhatnagar P Singh M Mishra S Kumar P Shukla Y Gupta KC Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
description	Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, India Abstract: In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF]) and green (epigallocatechin-3-gallate [EGCG]) tea in poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA)-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically) of mouse skin with either TF or EGCG (100 µg/mouse) doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk), 57.63% (1/10th of bulk), and 63.14% (1/5th of bulk) prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3) and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2) as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior ability to prevent DMBA-induced DNA damage at much lower concentrations, thus opening a new dimension in chemoprevention research. Keywords: DNA alkaline unwinding assay, mouse skin, DNA repair
format	article
author	Srivastava AK Bhatnagar P Singh M Mishra S Kumar P Shukla Y Gupta KC
author_facet	Srivastava AK Bhatnagar P Singh M Mishra S Kumar P Shukla Y Gupta KC
author_sort	Srivastava AK
title	Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
title_short	Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
title_full	Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
title_fullStr	Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
title_full_unstemmed	Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
title_sort	synthesis of plga nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced dna damage
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/6fefe448976343398e24f25f4a8a414e
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Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

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