Nanogel-based delivery system enhances PGE₂ effects on bone formation

Recovery of bone loss is one of the active research issues in bone medicine due to the need for efficient measures for bone gain. We examined here a novel drug delivery system using a nanogel of cholesterol-bearing pullulan (CHP) in combination with prostaglandin E₂ (PGE₂). PGE₂ or PGE₂/CHP, vehicle (saline containing 0.06% ethanol and 0.02% Tween 80) or CHP were injected on to the calvariae of mice once every day for 5 days per week for 4 weeks. Low dosage of PGE₂ (0.6 μg) alone or CHP alone did not induce new bone formation in this system. In contrast, PGE ₂ (0.6 μg)/ CHP induced new bone formation. Bone formation activities of PGE₂ was enhanced by CHP nanogelsonly at the site of injection (calvaria) but not in the distant sites of the skeleton, showing that PGE₂/CHP could avoid systemic effects. In spite of the fact that previously reported animal models of bone formation by PGE₂ were associated with loss of body weight, bone formation based on PGE ₂/CHPdid not associate with loss of body weight. Furthermore, only a single application of PGE₂ in combination with nanogel cross-linking hydrogel sphere (PGE₂/CHP-PEO) induced new bone formation. Thus, nanogel-based delivery system is an efficient delivery system of bone anabolic agent, PGE₂.