rhGALNS Enzyme Stability in Physiological Buffers: Implications for Sustained Release

Area of Science:

• Biochemistry
• Biomaterials Science
• Genetic Disorders

Background:

• Morquio A syndrome results from a deficiency in the GALNS enzyme, impairing glycosaminoglycan breakdown.
• Current recombinant human GALNS (rhGALNS) treatments involve costly, time-consuming intravenous infusions with limited efficacy.
• Developing a sustained-release injectable device could significantly improve patient quality of life.

Purpose of the Study:

• To investigate the stability of rhGALNS in physiological buffers and within polyethylene glycol (PEG) hydrogels.
• To assess the feasibility of using PEG hydrogels for sustained delivery of rhGALNS.

Main Methods:

• rhGALNS stability was tested in phosphate-buffered saline (PBS) and acidic buffer.
• Enzyme activity and hydrodynamic radius were measured after incubation in different conditions.
• rhGALNS was encapsulated in PEG hydrogels, and its activity was monitored during release over 7 days.

Main Results:

• rhGALNS activity decreased by 85% in PBS due to reversible inhibition, which was recoverable in acidic buffer.
• Incubation in PBS for 3 days caused an irreversible 85% loss of activity, without altering hydrodynamic radius.
• rhGALNS activity was retained upon encapsulation, with only a 20% decrease in specific activity over 7 days of release from the hydrogel.

Conclusions:

• rhGALNS is unstable in physiological buffers like PBS, hindering sustained delivery.
• Confinement within PEG hydrogels significantly enhances rhGALNS stability and activity retention.
• PEG hydrogels show promise as a delivery system for sustained release of rhGALNS and other enzymes unstable in vivo.