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 microg) alone or CHP alone did not induce new bone formation in this system. In contrast, PGE2 (0.6 microg)/CHP induced new bone formation. Bone formation activities of PGE2 was enhanced by CHP nanogels only 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 PGE2/CHP did 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.