Effect of crystallinity on in vitro and in vivo release behaviors of spherical self-assembly of rhIFN / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate effect of crystallinity on in vitro and in vivo release behaviors of spherical self-assembly of Recombinant human interferon-alpha (rhIFN). METHODS: rhIFN can form spherical self-assembly by static crystallization method. The crystallinity was determined by X-ray to characterize molecular ordered degree of various spherical crystals. The drug dissolution in vitro and the pharmacokinetics in vivo of various rhIFN forms were further investigated. RESULTS: The spherical self-assembly of rhIFN in amorphous and crystalline forms were obtained through adjusting protein supersaturation during self-assembly process. The amorphous precipitates were characterized as recovery of 96.5% and mean diameter size of 0.6 μm. Two kinds of crystallized rhIFN were characterized as mono-dispersed spheres, with yield of ≤ 80%, mean diameter size of 10-20 μm. Their crystallinity was 23.2% and 30.8%, respectively. The dissolving rates of spherical self-assemblies were decreased significantly with increased crystallinity. After s.c. administration of spherical self-assembly of rhIFN in amorphous and crystalline forms, the peak time (tmax) were retarded from(6.00±1.40) h to (13.20±2.68) and (22.40±3.57) h, the corresponding half life (t1/2) were prolonged from (4.75±0.82) h to (10.68±1.97) and (29.17±4.93) h. CONCLUSION: The spherical self-assemblies of rhIFN in crystalline form can improve their release performance either in vitro or in vivo, which provide a new candidate for sustained delivery of therapeutic proteins.