Enzyme loaded biodegradable microspheres in vitro ex vivo evaluation

Area of Science:

• Biochemistry
• Enzymology
• Drug Delivery Systems

Background:

• Prolidase deficiency (PD) is a rare autosomal recessive disorder.
• PD causes chronic, intractable skin ulcerations, especially on lower limbs.
• Current treatments for PD are insufficient, and a cure remains elusive.

Purpose of the Study:

• To investigate enzyme replacement therapy for PD using microencapsulated prolidase.
• To develop and characterize biodegradable prolidase-loaded microspheres.
• To assess the stability and activity of encapsulated prolidase.

Main Methods:

• Poly(D,L-lactide-co-glycolide) (PLGA) microspheres loaded with prolidase were prepared using a w-o-w double emulsion solvent evaporation method.
• In vitro characterization included morphological analysis, total protein content, and dissolution testing.
• Ex vivo evaluation of enzyme activity was performed on skin fibroblast extracts from healthy subjects and PD patients.

Main Results:

• Microencapsulation successfully stabilized prolidase activity within PLGA microspheres.
• Both in vitro and ex vivo studies demonstrated active enzyme release from the microspheres.
• The microparticulate systems showed potential for sustained enzyme delivery.

Conclusions:

• Microencapsulation is a viable strategy for stabilizing prolidase enzyme activity.
• This approach can lead to effective enzyme replacement therapy for prolidase deficiency.
• The developed formulation shows promise as a parenteral depot drug delivery system for PD treatment.