| Systemically delivered NELL-1, a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL1 (NELL-PEG) increases the half-life of the protein in a mouse model without compromising its osteogenic potential, thereby improving its pharmacokinetics upon systemic delivery. Weekly intravenous (IV) NELL-PEG injection significantly enhances overall bone properties. This study consists of a two-fold approach; a biodistribution test and an in vivo osteogenic potential test. The biodistribution test compared two commonly used administration methods for drug delivery other than IV -- intraperitoneal (IP) and subcutaneous (SC) -- to examine NELL-PEG biodistribution in mice. Compared to a single-dose SC injection (1.25 mg/kg), a single-dose IP administration yielded a higher protein uptake in the targeted bone sites. When the IP injection dose was doubled to 2.5 mg/kg, the protein remained in the femurs, tibias, and vertebrae for up to 72 hours. Next, based on the results of the biodistribution study, IP administration was selected to further investigate the in vivo osteogenic effects of weekly NELL-PEG injection (q7d). In vivo, the IP administered NELL-PEG group showed significantly greater bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular bone formation in the targeted bone sites compared to the PBS control. In summary, weekly NELL-PEG injection via IP administration successfully enhanced the overall bone quality. These findings demonstrate that systemic delivery of NELL-PEG via IP administration may serve as an effective osteogenic therapy for preventing and treating osteoporosis. |
