Comparison between Nanoparticle Encapsulation and Surface Loading for Lysosomal Enzyme Replacement Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Lysosomal storage disorders require enzyme replacement therapy.
• Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) are explored for enhanced enzyme delivery.
• Encapsulated versus coated enzyme-loaded NPs have not been directly compared.

Purpose of the Study:

• To compare the efficacy of encapsulated vs. coated PLGA NPs for delivering therapeutic enzymes.
• To evaluate NP formulation, stability, and targeting for lysosomal storage disorders.
• To assess enzyme delivery and therapeutic enhancement in vitro and in vivo.

Main Methods:

• Screening of PLGA co-polymers and surfactants for optimal NP characteristics.
• Formulation of encapsulated and coated NPs with hyaluronidase (HAse) and acid sphingomyelinase (ASM).
• Characterization of NP size, PDI, ζ potential, enzyme loading, stability, and cellular uptake in mice models.

Main Results:

• Optimized NPs demonstrated favorable characteristics (e.g., 181 nm diameter, -36 mV ζ potential).
• Encapsulated NPs showed higher enzyme loading and superior delivery efficiency compared to coated NPs.
• Both NP formulations were stable, internalized by cells, trafficked to lysosomes, and targeted organs, including the brain.

Conclusions:

• Encapsulated PLGA NPs are more effective than coated NPs for enzyme delivery in lysosomal storage disorders.
• This study provides critical guidance for developing nanoparticle-based enzyme replacement therapies.
• Targeted PLGA NPs demonstrate potential for treating both peripheral and central nervous system manifestations.