Protein release behavior from porous microparticle with lysozyme/hyaluronate ionic complex.
Porous microparticles (PMs) with a low density (<0.4 g/cm3) for pulmonary protein delivery were prepared by the water-in-oil-in-water (W1/O/W2) multi-emulsion method using a cyclodextrin derivative as a porogen. The complexation of positively charged lysozyme (Lys) and negative-charged hyaluronate (HA) was investigated for long-term protein release from PMs. The interaction of Lys and HA not only increased protein encapsulation efficiency but also stabilized Lys against a denaturing organic solvent (dichloromethane). Furthermore, PMs with Lys/HA complexes increased the Lys release period up to 7 days, as opposed to a 4h Lys release time from PMs without Lys/HA complexes. In particular, PMs containing 10mg of HA and 50mg of Lys showed almost zero-order Lys release kinetic for 7 days and preserved the bioactivity of Lys more than 98% during its entire release period. This result suggests that PMs with Lys/HA complexes may be applied in long-term pulmonary administration of protein or peptide drugs, including those that require particles to arrive at a deep lung epithelium with the help of low density (high porosity) of PMs.
Lee
Eun Seong
ES
Pharmaceutical & 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
Kwon
Min Jung
MJ
Na
Kun
K
Bae
Jun Ho
JH
D004655:Emulsions / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
D004655:Emulsions; D012710:Serum Albumin, Bovine; D006820:Hyaluronic Acid; D009113:Muramidase; D008239:Lysine