title: Efficacy of Intraperitoneal Administration of PEGylated NELL-1 for Bone Formation.
abstract: Systemically delivered NEL-like molecule-1 (NELL-1), a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL-1 (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. This study consists of a twofold 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 intravenous-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 h. 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, bone volume fraction, and trabecular bone formation in the targeted bone sites compared to the phosphate-buffered saline 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.
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Justine
authors.initials: J
authors.lastname: Tanjaya
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, Los Angeles, California.; Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, Pocheon, South Korea.; Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Soonchul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Shi
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.; Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Pia
authors.initials: P
authors.lastname: Ang
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Section of Oral and Maxillofacial Radiology, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tetradis
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.; Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, Los Angeles, California.; Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.; Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
authors.affiliation: Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California , Los Angeles, Los Angeles, California.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kwak
keywords: PEGylated NELL-1; biodistribution; bone formation; intraperitoneal administration; osteoporosis