Curcumin loaded mesoporous silica nanoparticles: assessment of bioavailability and cardioprotective effect

Drug Dev Ind Pharm. 2019 Dec;45(12):1889-1895. doi: 10.1080/03639045.2019.1672717. Epub 2019 Oct 7.

Abstract

Rhizomes of the plant Curcuma longa has been traditionally used in medicine and culinary practices in India. It possesses various pharmacological effect, namely, antioxidant, hepatoprotective, anti-inflammatory, anti-thrombosis, and anti-apoptotic. The study was undertaken to assess the effect of curcumin and curcumin loaded mesoporous silica nanoparticles (MSNs) against doxorubicin (DOX)-induced myocardial toxicity in rats. Furthermore, the study also included the bioavailability estimation of curcumin delivered alone and delivered via mesoporous technology. Cardiotoxicity was produced by cumulative administration of DOX (2.5 mg/kg for two weeks). Curcumin and curcumin loaded mesoporous nanoparticles (MSNs) each 200 mg/kg, po was administered as pretreatment for two weeks and then for two alternate weeks with DOX. The repeated administration of DOX induced cardiomyopathy associated with an antioxidant deficit and increased level of cardiotoxic biomarkers. Pretreatment with curcumin (alone and via MSNs) significantly protected myocardium from the toxic effects of DOX by significantly decreased the elevated level of malondialdehyde and increased the reduced level of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in cardiac tissue. MSNs based delivery was found superior compared to curcumin delivered alone. Moreover, the results of bioavailability assessment in rats clearly indicated higher Cmax and AUC values in rats when curcumin was administered via MSNs indicating superior bioavailability. The bioavailability of curcumin loaded MSNs, biochemical and histopathology reports support the good cardioprotective effect of curcumin which could be attributed to its increased bioavaibility lead to good antioxidant and anti-inflammatory activity.

Keywords: Cardiotoxicity; MSNs; RP-HPLC; bioavailability; curcumin.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacokinetics
  • Biological Availability
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacokinetics*
  • Cardiotoxicity / etiology
  • Cardiotoxicity / pathology
  • Cardiotoxicity / prevention & control*
  • Curcuma / chemistry
  • Curcumin / administration & dosage
  • Curcumin / pharmacokinetics*
  • Disease Models, Animal
  • Doxorubicin / toxicity
  • Drug Carriers / chemistry*
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Male
  • Myocardium / pathology
  • Nanoparticles / chemistry
  • Oxidative Stress / drug effects
  • Rats
  • Silicon Dioxide / chemistry

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cardiotonic Agents
  • Drug Carriers
  • Silicon Dioxide
  • Doxorubicin
  • Curcumin