Self-double-emulsifying drug delivery system was prepared by mixing water/oil emulsions with hydrophilic emulsifiers proportionally, which could self-emulsify into water/oil/water multiple emulsions followed by dilution with aqueous media under gastrointestinal motility or mild agitation at the ambient temperature. Nattokinase was encapsulated, then released in vitro and pharmacodynamics study in vivo.
Abstract:In the present study, we prepared nattokinase-loaded self-double-emulsifying drug delivery system (SDEDDS) and investigated its preliminary pharmacodynamics.The type and concentration of oil phase, inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS. Next, the optimum formulations were characterized based on microstructure, volume-weighted mean droplet size, self-emulsifying rate, yield, storage stability, in vitro release and in vivo pharmacodynamics studies. The water/oil/water multiple emulsions exhibited typical multiple structure, with relatively small volume-weighted mean droplet size 6.0 ± 0.7 µm and high self-emulsifying ability (self-emulsifying time <2 min). Encapsulation of nattokinase was up to 86.8 ± 8.2%. The cumulative release of nattokinase within 8 h was about 30%, exhibiting a sustained release effect. The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution. Moreover, we showed that SDEDDS could successfully self-emulsify into water /oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment. Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.