Pentablock copolymer dexamethasone nanoformulations elevate MYOC: In vitro liberation, activity and safety in human trabecular meshwork cells

Vibhuti Agrahari, Guorong Li, Vivek Agrahari, Iris Navarro, Kristin Perkumas, Abhirup Mandal, W. Daniel Stamer, Ashim K. Mitra

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aim: The aim of this study is to examine the elevation of MYOC in long-term treatment of human trabecular meshwork (HTM) cells using dexamethasone (DEX) encapsulated pentablock (PB) copolymer-based nanoparticles (NPs) (DEX-PB-NPs). Materials & methods: PB copolymers and DEX-PB-NPs were synthesized and characterized using nuclear magnetic resonance, gel permeation chromatography, and X-ray diffraction analyses. MYOC levels secreted from HTM cells were measured by western blot (WB) analysis. Results: DEX-PB-NPs were formulated in the size range of 109 ± 3.77 nm (n = 3). A long term DEX release from the NPs was observed over three months. Cell viability and cytotoxicity were not affected up to 12 weeks of treatment with PB-copolymer or DEX-PB-NPs. WB data from five HTM cell strains showed that MYOC levels increased by 5.2 ± 1.3, 7.4 ± 4.3, and 2.8 ± 1.1-fold in the presence of DEX-PB-NPs compared with 9.2 ± 3.8, 2.2 ± 0.5, and 1.5 ± 0.3-fold at 4, 8 and 12 weeks in control-DEX treatment group, respectively (n = 5). Based on the decline in MYOC levels after withdrawal of DEX from control wells, DEX-PB-NPs released the DEX for at least 10 weeks. Conclusion: The treatment of HTM cells using DEX-PB-NPs were analyzed in this study. The in vitro cell-based system developed here is a valuable tool for determining the safety and effects of steroids released from polymeric NPs.

Original languageEnglish (US)
Pages (from-to)1911-1926
Number of pages16
JournalNanomedicine
Volume12
Issue number16
DOIs
StatePublished - Aug 2017
Externally publishedYes

Keywords

  • block copolymer
  • MYOC
  • nanoparticle
  • steroids
  • sustained release
  • trabecular meshwork cells
  • western blot

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

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