Enhanced effects of low molecular weight heparin intercalated with layered double hydroxide nanoparticles on rat vascular smooth muscle cells

Surgical procedures to remove atherosclerotic lesions and restore blood flow also injure the artery wall, promoting vascular smooth muscle cell (SMC) phenotypic change, migration, proliferation, matrix production and ultimately, restenosis of the artery. Hence identification of effective anti-restenotic strategies is a high priority in cardiovascular research, and SMCs are a key target for intervention. This paper presents the in vitro study of layered double hydroxides (LDHs) as drug delivery system for an anti-restenotic drug (low molecular weight heparin, LMWH). The cytotoxicity tests showed that LDH itself had very limited toxicity at concentrations below 50 mu g/mL over 6-day incubation. LDH nanoparticles loaded with LMWH (LMWH LDHs) were prepared and tested on rat vascular SMCs. When conjugated to LDH particles, LMWH enhanced its ability to inhibit SMC proliferation and migration, with greater than above 60% reduction compared with the control (growth medium) over 3 or 7-day incubation. Cellular uptake studies showed that compared with LMWH alone, LMWH LDH hybrids were internalized by SMCs more rapidly, and uptake was sustained over a longer time, possibly revealing the mechanisms underlying the enhanced biological function of LMWH LDH. The results suggest the potential of LMWH LDH as an efficient anti-restenotic drug for clinical application. (C) 2010 Elsevier Ltd. All rights reserved.