Carrier-free low-molecular-weight heparin and lipid conjugate-based nano-anticoagulant with an albumin shuttling effect

Abstract The potential for polysaccharides to have long-term effects in the body is restricted by their naturally large molecular size and flexibility. In particular, patients receiving the anticoagulant heparin in preventive therapies would strongly benefit from an extended (long-term) effect of administered heparin, but the related technology has hardly been developed. Here, we have newly designed and evaluated a nanoengineered low-molecular-weight heparin (LMWH) and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of heparin activity via end-specific conjugation of the reducing end of heparin. It generates self-assembled nanoparticles (NP) with an average size of 105 ± 1.7 nm in water without any nanocarrier and, further, can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect such that the resulting molecules can circulate in the bloodstream for 4–5 days. We substantiate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis, offering novel insights. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.