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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3141–3151 | Cite as

Evaluation of Anti-Tumor Efficacy of Vorinostat Encapsulated Self-Assembled Polymeric Micelles in Solid Tumors

  • Sri Vishnu Kiran Rompicharla
  • Prakruti Trivedi
  • Preeti Kumari
  • Omkara Swami Muddineti
  • Sowmya Theegalapalli
  • Balaram Ghosh
  • Swati Biswas
Research Article
  • 59 Downloads

Abstract

Vorinostat (VOR), a potent HDAC inhibitor, suffers from low solubility and poor absorption, which hinders its successful application in therapy, especially in the treatment of solid tumors. In this study, an effort to improve the physicochemical characteristics of VOR was made by encapsulating it in PEG-PLGA copolymeric micelles. VOR-loaded PEG-PLGA micelles (VOR-PEG-PLGA) were produced by thin-film hydration and physicochemically characterized. The PEG-PLGA micelles had an average size of 124.06 ± 2.6 nm, polydispersity index of 0.27 ± 0.1, and entrapment efficiency of 90 ± 2.1%. Micelles were characterized by TEM, DSC, and drug release studies. The drug release occurred in a sustained manner up to 72 h from PEG-PLGA micelles. In the in vitro cell-based studies using human breast cancer (MDA MB 231) and murine melanoma (B16F10) cell lines, VOR-PEG-PLGA micelles exhibited superior cellular internalization, enhanced cytotoxic activity, and greater apoptosis compared to free drug. Percent cell killing of 54.9% for VOR-PEG-PLGA-treated cells was observed after 24 h compared to 36% for free VOR in MDA MB 231 cell line. Further, significant tumor suppression was witnessed in B16F10 tumor-bearing mice treated with VOR-PEG-PLGA micelles with a 1.78-fold reduction in tumor volume compared to free VOR-treated animals. Overall, the VOR-PEG-PLGA micelles improved the biopharmaceutical properties of VOR, which resulted in enhanced anti-tumor efficacy. Therefore, the newly developed nano-formulation of VOR could be considered as an effective treatment option in solid tumors.

KEY WORDS

polymeric micelles vorinostat drug delivery anticancer in vivo efficacy 

Notes

Acknowledgements

The authors acknowledge Evonik India Pvt. Ltd., Mumbai, India for the gift sample of Resomer RG504H. The authors also thank the Department of Biotechnology (Bio-CARe scheme, BT/Bio-CARe/07/10003/2013-2014) for funding.

Compliance with Ethical Standards

Conflict of Interest

Authors declare no conflict of interest.

Animal Studies

All institutional and national guidelines for the care and use of laboratory animals were followed.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Sri Vishnu Kiran Rompicharla
    • 1
  • Prakruti Trivedi
    • 1
  • Preeti Kumari
    • 1
  • Omkara Swami Muddineti
    • 1
  • Sowmya Theegalapalli
    • 1
  • Balaram Ghosh
    • 1
  • Swati Biswas
    • 1
  1. 1.Birla Institute of Technology and Science Pilani, Hyderabad CampusHyderabadIndia

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