C. Mancino (Houston, US)
Houston Methodist Research Institute Center for musculoskeletal regenerationPresenter Of 1 Presentation
P101 - Theranostic Nanoformulation Targets Post Traumatic Osteoarthritis Injuries in the Acute Phase
Abstract
Purpose
Post traumatic osteoarthritis (PTOA) is one of the most common defects of cartilage and a severe cause of disability. After injury, a local inflammatory response results in progressive joint degeneration, and immune cells infiltrate the inflamed synovium (macrophages play an important role in tissue homeostasis). Available treatments still lack effectiveness. Recent studies have shown increasing interest in the use of nanomedicine to develop Drug Delivery Systems (DDSs) for PTOA. Here, we assessed the targeting potential of liposome-based biomimetic nanoparticles (Orthosomes – ORTHO, featuring membranes of macrophages as building blocks) in a PTOA mouse model (dissection of medial meniscus - DMM), during the acute phase of inflammation.
Methods and Materials
Nanoparticles (NPs) were synthesized via thin layer evaporation and extrusion and characterized via dynamic light scattering. Cy7-labeled NPs were administered systemically at 24h, 48h, 72h, and 7d post-injury in a DMM mouse model, and organs and legs were imaged with IVIS.
Results
6h post-NPs administration (size: 100 nm, PDI < 0.15, and surface charge below -40mV), IVIS showed significantly higher accumulation of ORTHO within the injured leg for up to 7 days post-injury. We evaluated NPs’ biodistribution ex vivo: as expected, preferential accumulation of ORTHO occurred in filtering organs, the highest signal being in the liver, kidneys, spleen, lungs. Finally, we qualitatively demonstrated progressive accumulation of NPs in the injury site via intravital microscopy, following the signal of Cy5.5 labeled ORTHO from 15min to 6h post-injection in the DMM group.
Conclusion
Taken together, these findings point towards a revolution of the traditional clinical approaches to treat PTOA: we have demonstrated that these NPs can be used to identify injury sites, fulfilling the need for a diagnostic tool. In addition, the versatility of these DDSs allows them to be potential candidates for encapsulating a variety of drugs, making them a promising theranostic tool for treatment of PTOA.
Presenter Of 1 Presentation
P101 - Theranostic Nanoformulation Targets Post Traumatic Osteoarthritis Injuries in the Acute Phase
Abstract
Purpose
Post traumatic osteoarthritis (PTOA) is one of the most common defects of cartilage and a severe cause of disability. After injury, a local inflammatory response results in progressive joint degeneration, and immune cells infiltrate the inflamed synovium (macrophages play an important role in tissue homeostasis). Available treatments still lack effectiveness. Recent studies have shown increasing interest in the use of nanomedicine to develop Drug Delivery Systems (DDSs) for PTOA. Here, we assessed the targeting potential of liposome-based biomimetic nanoparticles (Orthosomes – ORTHO, featuring membranes of macrophages as building blocks) in a PTOA mouse model (dissection of medial meniscus - DMM), during the acute phase of inflammation.
Methods and Materials
Nanoparticles (NPs) were synthesized via thin layer evaporation and extrusion and characterized via dynamic light scattering. Cy7-labeled NPs were administered systemically at 24h, 48h, 72h, and 7d post-injury in a DMM mouse model, and organs and legs were imaged with IVIS.
Results
6h post-NPs administration (size: 100 nm, PDI < 0.15, and surface charge below -40mV), IVIS showed significantly higher accumulation of ORTHO within the injured leg for up to 7 days post-injury. We evaluated NPs’ biodistribution ex vivo: as expected, preferential accumulation of ORTHO occurred in filtering organs, the highest signal being in the liver, kidneys, spleen, lungs. Finally, we qualitatively demonstrated progressive accumulation of NPs in the injury site via intravital microscopy, following the signal of Cy5.5 labeled ORTHO from 15min to 6h post-injection in the DMM group.
Conclusion
Taken together, these findings point towards a revolution of the traditional clinical approaches to treat PTOA: we have demonstrated that these NPs can be used to identify injury sites, fulfilling the need for a diagnostic tool. In addition, the versatility of these DDSs allows them to be potential candidates for encapsulating a variety of drugs, making them a promising theranostic tool for treatment of PTOA.