Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro liberation, activity and safety in human trabecular meshwork cells. (August 2017)

• Record Type: Journal Article
• Authors: Agrahari, Vibhuti; Li, Guorong; Agrahari, Vivek; Navarro, Iris; Perkumas, Kristin; Mandal, Abhirup; Stamer, W Daniel; Mitra, Ashim K
• Is Part Of: Nanomedicine. Volume 12:Number 16(2017)
• Page Start: 1911
• Page End: 1926
• Publication Date: 2017-08
• Subjects: block copolymer -- MYOC -- nanoparticle -- steroids -- sustained release -- trabecular meshwork cells -- western blot; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2017-0140
• Languages: English
• ISSNs: 1743-5889

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.