Bone-targeted and redox-responsive polymeric nanomicelles based on hyaluronic acid.

Systemic drug administration usually results in low drug accumulation in bone tissue and causes toxicity and side effects. A promising method is the synthesis of bone tissue-targeting nanocarriers that are smart in response to the cancer environment. To achieve this goal, polymeric nanomicelles composed of hyaluronic acid (HA), alendronate (ALN), dithiodipropionic acid (DPA, containing disulfide bond -SS-), and hexadecanol (C) were prepared for curcumin (CUR) delivery. This bone tissue-targeting and redox-sensitive amphiphilic polymer was synthesized in three steps and then characterized by HNMR and FTIR tests. The critical micelle concentration for the prepared polymer (HA-ALN-SS-C) was 13.95 µg/mL to form stable nanomicelles. The formed nanomicelles exhibited a spherical structure with an average size of 114 nm. The drug loading amount of nanomicelles across various drug-to-polymer ratios ranged from 5.00 to 11.06 %, and the drug encapsulation efficiency was from 52.63 % to 41.45 %. The bone tissue-targeting efficiency was determined using the hydroxyapatite (HAp) adsorption test, which showed that a higher ALN ratio in the HA-ALN-SS-C system led to higher HAp adsorption. In vitro drug release tests conducted in tumor-simulated environments with varying Glutathione (GSH) concentrations exhibit the release sensitivity of nanomicelles to both GSH levels and the disulfide bond ratios within the polymer structures. Reb blood hemolysis assay and cytotoxicity tests on fibroblast cells showed that these polymeric nanomicelles were blood-compatible and non-toxic. Additionally, cytotoxicity tests on MDA-MB-231 cell lines confirmed the nanomicelles' ability to enhance the cytotoxic efficiency of the encapsulated drug.