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Drug Delivery and Translational Research

, Volume 9, Issue 5, pp 867–878 | Cite as

Effect of formulation parameters on pharmacokinetics, pharmacodynamics, and safety of diclofenac nanomedicine

  • Dhanya Narayanan
  • Gopikrishna J. Pillai
  • Shantikumar V. NairEmail author
  • Deepthy MenonEmail author
Original Article
  • 77 Downloads

Abstract

This study reports the development of a nanoformulation of diclofenac sodium, a potent non-steroidal anti-inflammatory drug, at its clinical dose, utilizing a FDA approved polymer, hydroxyethyl starch. The study specifically focused on the control of pharmacokinetics, pharmacodynamics, and biodistribution by particle surface functionalization and alteration of excipient levels in the final formulation. Stable diclofenac sodium–loaded hydroxyethyl starch nanoparticles (nanodiclo) of size 170 ± 5 nm and entrapment efficiency 72 ± 3% were prepared. Free diclofenac, nanodiclo, nanodiclo surface functionalized by PEGylation, nanodiclo with excipients removed, and finally PEGylated nanodiclo with excipients removed were all tested comparatively at two different doses. The results showed substantial impact of both excipients and PEGylation on the pharmacokinetics and pharmacodynamics in vivo. Further, the results proved that excipient removed PEGylated nanodiclo at lower dose achieved clinical therapeutic levels in blood for up to 120 h, with minimal accumulation in critical organs, and much better efficacy than other controls.

Keywords

Diclofenac sodium Excipients Hydroxyethyl starch nanoparticles Pharmacokinetics Pharmacodynamics 

Notes

Acknowledgments

Authors gratefully acknowledge Centre for Nanosciences and Molecular Medicine, Amrita Viswavidyapeetham, for providing the infrastructure for the successful completion of this work. Thanks to Themis Medicare for providing the drug diclofenac sodium, to Mr. Sajin P Ravi for SEM analysis, and to Dr. AKK Unni, Dr. Reshmi P, Mr. Sunil, Mr. Sajith, and Mrs. Sunitha for their help with animal studies.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed. The experiments comply with the current laws of the country in which they were performed. All animal experiments were carried out after obtaining ethical approval from the Institutional Animal Ethical Committee of Amrita Institute of Medical Sciences & Research Centre, Kochi, India.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13346_2018_614_MOESM1_ESM.docx (29 kb)
ESM 1 (DOCX 28 kb)

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Centre for Nanosciences & Molecular MedicineAmrita Institute of Medical Sciences & Research CentreKochiIndia

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