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

Nanomedicine (Lond). 2017 Aug;12(16):1911-1926. doi: 10.2217/nnm-2017-0140. Epub 2017 Jul 31.

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.

Keywords: MYOC; block copolymer; nanoparticle; steroids; sustained release; trabecular meshwork cells; western blot.

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / chemistry*
  • Cell Survival
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism*
  • Dexamethasone / administration & dosage
  • Dexamethasone / chemistry*
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Drug Carriers / toxicity
  • Drug Compounding
  • Drug Liberation
  • Eye Proteins / metabolism*
  • Glycoproteins / metabolism*
  • Humans
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Prostaglandins A / chemistry
  • Surface Properties
  • Trabecular Meshwork / drug effects*
  • Trabecular Meshwork / metabolism

Substances

  • Adrenal Cortex Hormones
  • Cytoskeletal Proteins
  • Drug Carriers
  • Eye Proteins
  • Glycoproteins
  • Polyesters
  • Prostaglandins A
  • trabecular meshwork-induced glucocorticoid response protein
  • polycaprolactone
  • Polyethylene Glycols
  • Dexamethasone