Development of dextran microparticles loaded with IL-IRa of high-encapsulation efficiency and high-bioactivity by a novel method without exposing IL-IRa to water-oil interfaces

摘要

The interleukin-1 receptor antagonist (IL-IRa), having the potential of treating cancers, has been used for treating rheumatoid arthritis in clinic. To improve its therapeutic efficacy and patient compliance, IL-IRa was of ten needed to prepare a long efficacy formulation using all kinds of method for protein stabilization. In this study, we reported a novel freezing-induced PEG water solution phase/dextran water solution phase separation method to prepare the IL-1 Ra-loaded dextran microparticles to address stability of IL-IRa in preparation process for all kinds of formulation, namely: first IL-IRa was dissolved in water together with dextran and polyethylene glycol, and then by a freezing process during which dextran is separated out as the dispersed phase with IL-IRa partitioned in dextran microparticles preferentially. The frozen sample was then lyophilized to powder and washed with dichloromethane to remove the PEG continuous phase. Once IL-Ra was loaded in the dextran microparticles, 1-5 μm in diameter, the dextran microparticles gained resistance to oil/water interfaces without IL-Ra aggregation and activity loss. The bioactivity from dextran microparticles in vitro is preserved highly (above 98%), while bioactivity from IL-lRa-loaded dextran microparticles using the control method of water-in-oil-in-water (W/O/W) method is only 70.5% by inhibiting melanoma B16 cell proliferation. The dextran microparticles may be used further to prepare different formulations according to clinic heeds.