Biodegradable polyethylene glycol hydrogels for sustained release and enhanced stability of rhGALNS enzyme

Era Jain, Michael Flanagan, Saahil Sheth, Shiragi Patel, Qi Gan, Birju Patel, Adriana M. Montaño, Silviya P. Zustiak

Research output: Contribution to journalArticle

Abstract

Mucopolysaccharidosis IVA (Morquio A disease) is a genetic disorder caused by deficiency of N-acetylgalactosamine-6-sulfate-sulfatase (GALNS), leading to accumulation of keratan sulfate and chondroitin-6-sulfate in lysosomes. Many patients become wheelchair-dependent as teens, and their life span is 20–30 years. Currently, enzyme replacement therapy (ERT) is the treatment of choice. Although it alleviates some symptoms, replacing GALNS enzyme poses several challenges including very fast clearance from circulation and instability at 37 °C. These constraints affect frequency and cost of enzyme infusion and ability to reach all tissues. In this study, we developed injectable and biodegradable polyethylene glycol (PEG) hydrogels, loaded with recombinant human GALNS (rhGALNS) to improve enzyme stability and bioavailability, and to sustain release. We established the enzyme’s release profile via bulk release experiments and determined diffusivity using fluorescence correlation spectroscopy. We observed that PEG hydrogels preserved enzyme activity during sustained release for 7 days. In the hydrogel, rhGALNS diffused almost four times slower than in buffer. We further confirmed that the enzyme was active when released from the hydrogels, by measuring its uptake in patient fibroblasts. The developed hydrogel delivery device could overcome current limits of rhGALNS replacement and improve quality of life for Morquio A patients. [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalDrug Delivery and Translational Research
DOIs
StateAccepted/In press - Jan 1 2020
Externally publishedYes

Keywords

  • Bioactivity
  • Enzyme replacement therapy
  • Enzyme stability
  • GALNS
  • Hydrogel
  • Morquio A disease
  • Polyethylene glycol
  • Sustained release

ASJC Scopus subject areas

  • Pharmaceutical Science

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