Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage
Authors: Madhulika Singh
Pradeep Kumar
Priyanka Bhatnagar
Yogeshwer Shukla
Sanjay Mishra
Amit Kumar Srivastava
Kailash Chand Gupta
Journal: International Journal of Nanomedicine (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA alkaline unwinding assay; DNA repair; mouse skin.

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. 

Retracted: No

PubPeer comments:
 Figure 6 u201cEffect of bulk and PLGA-loaded tea polyphenols on the transcription of DNA damage responsive genes. The pixel density of the specific mRNA expression bands was quantified by densitometry and expressed as a fold difference against u03b2-actin.u201d ![file] ![file] Figure 7 u201cEffect of bulk and PLGA-loaded tea polyphenols on the transcription of DNA repair responsive genes. The pixel density of the specific mRNA expression bands was quantified by densitometry and expressed as a fold difference against u03b2-actin.u201d ![file] , 
 Erratum published 5 August 2019: https: www.dovepress.com erratum-synthesis-of-plga-nanoparticles-of-tea-polyphenols-and-th-peer-reviewed-article-IJN  Upon reviewing the article, the authors noticed the PCR gel images were difficult to view in Figures 6 and u200band 7 (pages 1458 and 1459). The authors confirm that the higher resolution figures provided do not impact the findings of the study. Figures 6 and u200band 7 should be presented as follows: ![file] ![file] The new Figures 6 and 7 are not  higher resolution or less  difficult to view . They re just different, without the distinctive bubbles of the original versions. ,