Development of Smoothened Agonist Nonphospholipid Liposomal Nanoparticles for Bone Repair
Abstract
Non-healing bone injuries represent a source of morbidity for combat casualties and military veterans, exacting both a devastating individual toll on the lives affected as well as an enormous socioeconomic burden. The manipulation of Hedgehog (Hh) signaling is a promising alternative for improved bone regeneration. In particular, the Hh activating small molecule SAG targets bone and vascular formation to induce bone healing. The present study seeks to develop a nanoparticle packaged Hh small molecule for use as a widely applicable bone graft substitute. To achieve this, we developed a novel class of liposomes formulated with single-chain amphiphiles and high content of sterols (sterosomes), resulting in significantly increased nanoparticle stability compared to conventional phospholipid. We then immobilized the sterosome onto the surface of poly (lactic-co-glycolic acid) scaffolds using dopamine intermediates to achieve controlled drug delivery in the defect site. Results showed that SAG-loaded liposomes induced a significant and dose-dependent increase in Hh-mediated osteogenic differentiation and calvarial bone healing. Favorable outcomes were achieved in comparison to standards of care, including collagen sponge delivered rBMP2 or allograft bone. This study suggests a useful nanocarrier design loading bioactive agents into functional non-phospholipid bilayers to improve clinical efficacy of current therapeutic agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2022
- Accession Number
- AD1191128
Entities
People
- Min Lee
Organizations
- University of California, Los Angeles