In vitro Preparation and Evaluation of Alendronate-modified Hyaluronic acid-based Nanomicelles as a Bone-Targeted Drug delivery system

Nanomicelles based on Hyaluronic acid (HA), a linear polysaccharide with high affinity to the CD44 receptor on cancerous cells, offer considerable potential to transport drugs to the target tissue while reducing exposure to normal tissues. The high affinity of alendronate (ALN) to hydroxyapatite crystals, the crucial component of bone, makes it an ideal candidate for bone-targeted delivering therapeutic nanoparticles. Here, we developed targeted and self-assembled nanocarriers by modifying HA nanomicelles with ALN to attach to hydroxyapatite. Curcumin (CUR), as a hydrophobic model drug, was used to evaluate the efficiency of developed nanomicelles. The size of blank and CUR-loaded nanomicelles was below 200 nm and their critical micelle concentrations were in the range of 38 mu g/ml, which is suitable for delivery to bone tissue. The CUR-loaded ALN-HA-AC (CUR@ALN-HAAC) nanomicelles showed a two-step release pattern, a first accelerated release period (12 % in 1 h) followed by a sustained release (65 % up to 50 h). The hydroxyapatite affinity experiment indicated that CUR@ALN-HA-AC nanomicelles exhibited significantly high affinity to the bone. Cytotoxicity studies on MG-63 cell lines demonstrated that CUR-loaded micelles exhibited much higher cytotoxic activity compared to free CUR, indicating that encapsulation in HA-ALN-AC micelles significantly enhanced the tumor cell-killing ability of CUR.