In vitro/in vivo correlation for 14C-methylated lysozyme release from poly(ether-ester) microspheres

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Sustained protein delivery is crucial for therapeutic efficacy.
• Polymeric microspheres offer a promising platform for controlled drug release.
• Poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) copolymers are investigated for their potential in drug encapsulation and release.

Purpose of the Study:

• To establish an in vitro/in vivo correlation for sustained protein release from PEGT/PBT microspheres.
• To evaluate the release kinetics of a model protein (lysozyme) from various PEGT/PBT formulations.
• To assess the predictability of in vitro release data for in vivo performance.

Main Methods:

• Lysozyme was radiolabeled and encapsulated into PEGT/PBT microspheres using a water-in-oil-in-water emulsion technique.
• Microsphere formulations with varying copolymer compositions were prepared.
• Subcutaneous administration of microspheres to rats, followed by plasma analysis for radioactivity.
• In vitro release studies conducted in phosphate-buffered saline.

Main Results:

• Encapsulation efficiencies ranged from 60-87%.
• In vitro release of lysozyme occurred over 14-28 days without an initial burst, dependent on PEG segment length and PEGT weight percentage.
• Radioactivity in rat plasma mirrored in vitro release profiles, with high correlation coefficients (>0.96).
• Minimal residual radioactivity (<10%) at the injection site after 28 days indicated no significant protein retention.

Conclusions:

• An excellent in vitro/in vivo correlation was achieved for lysozyme release from PEGT/PBT microspheres.
• The congruence between in vitro and in vivo release was independent of the specific release rate.
• These findings validate PEGT/PBT microspheres as a reliable system for sustained protein delivery with predictable release characteristics.