In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Aristides Tagalakis, Shivam Madaan, Scott D. Larsen, Richard R. Neubig, Peng T. Khaw, Cynthia Yu-Wai-Man

Research output: Contribution to journalArticle

5 Citations (Scopus)
59 Downloads (Pure)

Abstract

Background: Sustained drug delivery is a great unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results: The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions: Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.
Original languageEnglish
JournalJournal of Nanobiotechnology
Volume16
Issue number97
Early online date27 Nov 2018
DOIs
Publication statusE-pub ahead of print - 27 Nov 2018

Keywords

  • Nanocarrier
  • Sustained release
  • Inhibitor
  • Glaucoma
  • Fibrosis

Fingerprint Dive into the research topics of 'In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis'. Together they form a unique fingerprint.

  • Cite this