Surface charge driven polymeric drug carrier for bone specific delivery of estradiol: in vitro and in vivo assessment

Osteoporosis is a systemic skeletal disease affecting postmenopausal women worldwide. Adverse side effects are associated with long term conventional hormone therapy in osteoporosis treatment. Estradiol was loaded in PLGA nanoparticles coated with polyethylene imine to impart positive surface charge to preferentially localize hormone in the negative surface of bone environment evading unwanted side effects. Nanoparticles prepared by emulsion solvent evaporation method were smaller than 200 nm with a surface charge of 35mV. In vitro hydroxyapatite binding studies revealed superior binding of 82% by polycationic particles compared to meagre 28% by plain PLGA nanoparticles. In vivo biodistribution studies in mice displayed nearly 3 fold higher bone uptake by cationic nanoparticles compared to plain PLGA system at 24 hours. Hematological and histological evaluation in acute toxicity study showed safe and nontoxic nature of cationic nanoparticles.. Higher C max , AUC 0-inf , t 1/2 values and lower clearance values was observed with nanoparticles compared to estradiol solution which can potentially lower frequency of administration compared to plain drug solutions. The osteoprotective effect of estradiol in cationic nanoparticles was established in ovariectomised rats. The osteotropic, nontoxic cationic nanoparticles can be considered a prototype for delivery of plethora of antiresoptive/anabolic agents to the skeletal environment.