Sulfated polysaccharide heparin used as carrier to load hydrophobic lappaconitine

•LA is simple to self-assemble into LMWH to form pH-sensitivity LMWH-LA.•LMWH has a superior loading capacity of 24.3% (w/w).•LMWH is a good template and has great potential to achieve synergistic effect of LA.•LMWH-LA effectively resolves the late onset time and the short duration of LA.

One-step self-assembly was used to prepare pH-sensitive lappaconitine-loaded low-molecular-weight heparin (LMWH-LA) and to demonstrate that the sulfur group promotes dissolution and has synergistic effect on the analgesic property of lappaconitine (LA). The LMWH-LA was characterized in terms of releasing behavior, pH-sensitivity, analgesic activity and anticoagulation property. The drug loading level of LA in low-molecular-weight heparin (LMWH) reached 24.3% (w/w). The LA, self-assembled in LMWH, released faster in an acidic environment than that in neutral or alkaline environments. Analgesic experiments showed that the LMWH-LA had earlier onset time and longer duration than the LA. Compared with LMWH, the LMWH-LA can reduce clotting time more effectively. These results suggest that the LMWH is a good template and has great potential to achieve synergistic effect of LA. In addition, similar macromolecular structure can be used as a new natural polymeric carrier for loading hydrophobic alkaloids.

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