Preparation and evaluation of nattokinase-loaded self-double-emulsifying drug delivery system

Abstract

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.

Recent Advances in Nattokinase-Enriched Fermented Soybean Foods: A Review

“…High self-double-emulsifying nano emulsions with NK showed a slow-release effect; the encapsulation rate of NK was 86.8 ± 8.2%. The cumulative release after 8h was about 30% [132]. Conjugated poly (lactic-co-glycolic acid) encapsulated NK also works as an effective drug for AD, with a cumulative release rate of 80.23% ± 3.675% over 24 h [133].…”

Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

“…SDNEDDSs undergo self-emulsification to w/o/w double nano-emulsion upon aqueous dispersion in the GI tract [ 302 ]. SDNEDDSs can save protein and other macromolecular drugs from enzymatic degradation in the GI tract, improve efficacy and reduce the drug dose [ 303 , 304 , 305 ]. However, the drug stability in the inner water phase always represent a challenge.…”

The Science of Selecting Excipients for Dermal Self-Emulsifying Drug Delivery Systems

“…Considering the summary provided in the table, it can be concluded that spontaneous emulsification is a valuable tool that should be investigated and optimized to the fullest. Therefore, this current work aims to equip the reader with an improved understanding of excipients needed to generate both dermal SEDDSs and SDEDDSs as well as the refinement of these drug delivery systems by discussing the inclusion of excipients such as thickening agents, emollients, humectants, preservatives, antioxidants, and co-solvents [5,12,[16][17][18][19][20].…”