Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria

Anjali Sharma, Ghareb M. Soliman, Noura Al-Hajaj, Rishi Sharma, Dusica Maysinger, Ashok Kakkar

Research output: Contribution to journalArticle

Abstract

Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory-Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria- targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

Original languageEnglish (US)
Pages (from-to)239-252
Number of pages14
JournalBiomacromolecules
Volume13
Issue number1
DOIs
StatePublished - Jan 9 2012
Externally publishedYes

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coenzyme Q10
Coenzymes
Mitochondria
Micelles
Polycaprolactone
Polymers
Pharmaceutical Preparations
Oxidative stress
Confocal microscopy
Ring opening polymerization
Pathology
Bromides

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria. / Sharma, Anjali; Soliman, Ghareb M.; Al-Hajaj, Noura; Sharma, Rishi; Maysinger, Dusica; Kakkar, Ashok.

In: Biomacromolecules, Vol. 13, No. 1, 09.01.2012, p. 239-252.

Research output: Contribution to journalArticle

Sharma, Anjali ; Soliman, Ghareb M. ; Al-Hajaj, Noura ; Sharma, Rishi ; Maysinger, Dusica ; Kakkar, Ashok. / Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria. In: Biomacromolecules. 2012 ; Vol. 13, No. 1. pp. 239-252.
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