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Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors

A Correction to this article was published on 06 May 2020

This article has been updated

Abstract

To promote the specific targeting and elimination of CD44-positive cancer cells, berberine chloride (BRB)-encapsulated hyaluronic acid-grafted poly(lactic-co-glycolic acid) copolymer (BRB-d(HA)-g-PLGA) nanoparticles (NPs) were prepared. The targeted action of these NPs was compared to non-targeted BRB-loaded PLGA NPs and bulk BRB. The in vitro studies demonstrated faster release of BRB and increased cytotoxicity of BRB-d(HA)-g-PLGA NPs in Hela and MCF-7 cells in comparison to BRB-PLGA NPs and bulk BRB. The uptake of BRB-d(HA)-g-PLGA NPs was increased in case of MCF-7 cells as compared to HeLa cells owing to the higher expression of CD44 receptors on MCF-7 cells. The CD44 receptor-mediated uptake of these NPs was confirmed through competitive inhibition experiments. The in vitro results were further validated in vivo in Ehrlich Ascites Carcinoma (EAC)-bearing mice. EAC-bearing mice were injected intravenously with these NPs and the results obtained were compared with that of BRB-PLGA NPs and bulk BRB. BRB-d(HA)-g-PLGA NPs were found to significantly enhance apoptosis, sub-G1 content, life span, mean survival time, and ROS levels in EAC cells with subsequent decrease in mitochondrial membrane potential and tumor burden ion tumor-bearing mice. Taking into account the findings of in vitro and in vivo studies, the enhanced and targeted anti-tumor activity of HA-grafted PLGA copolymer-encapsulated NPs of BRB cannot be negated. Therefore, HA-grafted nanoparticle-based delivery of BRB may offer a promising and improved alternative for anti-tumor therapy.

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  • 06 May 2020

    In the original article, there are inadvertent errors in Fig. 1(a) and Fig. 5(a) A and J. The corrected figures do not change the conclusions, text of the article, or figure legends.

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Acknowledgments

PB gratefully acknowledges the CSIR, New Delhi, India, for the award of a Senior Research Fellowship to carry out this work. KCG thanks ICMR, New Delhi, India, for awarding the Distinguished Scientist Chair at CSIR-IGIB, Delhi.

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Correspondence to K. C. Gupta.

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Bhatnagar, P., Kumari, M., Pahuja, R. et al. Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors. Drug Deliv. and Transl. Res. 8, 565–579 (2018). https://doi.org/10.1007/s13346-018-0485-9

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  • DOI: https://doi.org/10.1007/s13346-018-0485-9

Keywords

  • Berberine
  • Nanotechnology
  • Ehrlich ascites tumor