Development of Smoothened Agonist Nonphospholipid Liposomal Nanoparticles for Bone Repair
Technical Report,15 Jul 2018,14 Jul 2019
University of California Los Angeles United States
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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 very limited permeability and significantly increased nanoparticle stability compared to conventional phospholipid. The validity of sterosome nanoparticles was ensured by hydrodynamic characterizations before progression to scaffold loading and in vivo application. Sterosome was consistently bioactive and its osteoinductive potential was verified by staining and colorimetric assay. We then developed astrategy to immobilize sterosome onto the surface of poly lactic-co-glycolic acid PLGA scaffolds using dopamine intermediates to achieve controlled drug delivery in the defect site. This system will be advantageous for delivery of small molecular drugs such as SAG.
- Medicine and Medical Research