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Protein release behavior from porous microparticle with lysozyme/hyaluronate ionic complex.

Eun Seong Lee1, Min Jung Kwon, Kun Na

  • 1Pharmaceutical & Health Research Institute, Amore Pacific Corporation/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea. hejulu@hanmail.net

Colloids and Surfaces. B, Biointerfaces
|December 21, 2006
PubMed
Summary

Porous microparticles (PMs) were developed for long-term pulmonary protein delivery. Complexing lysozyme (Lys) with hyaluronate (HA) in PMs extended protein release to 7 days while preserving bioactivity.

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Area of Science:

  • Materials Science
  • Biotechnology
  • Pharmaceutical Sciences

Background:

  • Pulmonary drug delivery offers direct access to the lungs for treating respiratory diseases and systemic conditions.
  • Achieving sustained protein release from inhaled particles remains a challenge for effective long-term pulmonary therapies.

Purpose of the Study:

  • To develop low-density porous microparticles (PMs) for enhanced pulmonary protein delivery.
  • To investigate the complexation of lysozyme (Lys) and hyaluronate (HA) for sustained protein release and stabilization.
  • To evaluate the in vitro release kinetics and bioactivity preservation of proteins encapsulated within these PMs.

Main Methods:

  • Fabrication of porous microparticles using a water-in-oil-in-water (W1/O/W2) multi-emulsion method with a cyclodextrin derivative.
  • Complexation of positively charged lysozyme with negatively charged hyaluronate to form protein complexes.
  • Encapsulation of Lys/HA complexes into PMs and assessment of protein loading and stability.
  • In vitro release studies and bioactivity assays of lysozyme from PMs over an extended period.

Main Results:

  • Porous microparticles with low density (<0.4 g/cm3) were successfully prepared.
  • Lys/HA complexation significantly increased protein encapsulation efficiency and stabilized lysozyme against organic solvents.
  • PMs loaded with Lys/HA complexes demonstrated sustained lysozyme release for up to 7 days, compared to 4 hours without complexation.
  • Optimized PMs (10mg HA, 50mg Lys) exhibited near zero-order release kinetics and maintained over 98% lysozyme bioactivity throughout the 7-day release period.

Conclusions:

  • Porous microparticles incorporating lysozyme/hyaluronate complexes are effective for long-term pulmonary protein delivery.
  • The developed system enhances protein stability and achieves sustained release, crucial for pulmonary administration.
  • These findings suggest potential application in delivering protein or peptide drugs to the deep lung epithelium for chronic conditions.