Controlled curcumin release via conjugation into PBAE nanogels enhances mitochondrial protection against oxidative stress

Prachi Gupta, Carolyn T. Jordan, Mihail I. Mitov, D. Allan Butterfield, J. Zach Hilt, Thomas D. Dziubla

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Mitochondria are considered to be the “power plants” of the cell, but can also initiate and execute cell death, stimulated by oxidative stress (OS). OS induced mitochondrial dysfunction is characterized by a loss in oxygen consumption and reduced ATP production. Curcumin, as a potential therapeutic, has been explored as a candidate for mitochondrial OS suppression, but rapid metabolism and aqueous insolubility has prevented it from being effective. Further, efficient delivery of curcumin via the incorporation into nanocarriers has again been limited due to low drug loading capacities and/or significant burst release, resulting in acute cytotoxicity. Hence, to increase the therapeutic potential and reduce the toxic effects of curcumin, curcumin conjugated poly(β-amino ester) nanogels (CNGs) were synthesized using Michael addition chemistry. This approach provided easy control over the nanogel size, with CNGs showing a uniform release of active curcumin over 48h with no burst release. This controlled release system significantly increased the safety limit for curcumin, with a ten fold increase in the cytotoxic threshold, as compared to free curcumin. Further, real-time mitochondrial response analysis with the Seahorse XF96 showed effective and prolonged suppression of H2O2 induced mitochondrial oxidative stress upon pre-treating endothelial cells with CNGs and this potential of nanogels was studied at different pre-treatment times prior to H2O2 exposure.

Original languageEnglish
Pages (from-to)1012-1021
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume511
Issue number2
DOIs
StatePublished - Sep 25 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.

Keywords

  • Curcumin release
  • Nanogels
  • Poly(β-amino esters)
  • Seahorse bioscience XF96

ASJC Scopus subject areas

  • Pharmaceutical Science

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