Development and Characterization of Magnetic Nanoemulsion-Based Senolytic Peptides for Osteoarthritis Treatment.

The formulation and characterization of a novel nanoemulsion (NE) delivery system for senomodulator peptides aimed at enhancing the treatment of osteoarthritis (OA) are reported, in combination with magnetic nanoparticles (MNPs), for improving targeted delivery and traceability. Osteoarthritis, a prevalent degenerative joint disease associated with aging, is currently not effectively treated by disease-modifying therapies, posing a consistent health burden on individuals and healthcare systems worldwide. Existing treatments, such as nonsteroidal anti-inflammatory drugs and intra-articular injections, are limited by inadequate local drug concentrations and rapid clearance, often necessitating costly joint replacement. Lipid-based NE composed of biocompatible and biodegradable vitamin E and sphingomyelin, associated with the senolytic peptide NE:TUB1, is able to target senescent cells implicated in OA progression. Improved cellular retention and therapeutic effects of the associated TUB1 peptide, compared to its free form, have been demonstrated, suggesting a significant enhancement in therapeutic potential. The incorporation of MNPs to obtain NE:TUB1-MNP formulations offers the advantage of being traceable in vivo through clinically available imaging technologies, with the potential to enhance targeting capabilities through magnetic guidance. The characterization of NE:TUB1-MNPs involved the assessment of their physical and chemical properties, interaction with cells, cytotoxicity profile, and nanoparticle uptake in vitro using human primary adipose-derived stem cells. NE and NE:TUB1-MNP are shown to be stable, non-toxic, and capable of efficient intracellular uptake. The inclusion of MNPs not only supports cell viability and proliferation but also facilitates medium and long-term product traceability within joints, offering a promising approach for localized treatment. The enhanced anti-senescent role of NE:TUB1-MNP formulations are highlighted, suggesting their potential utility in mitigating OA progression and possibly other degenerative diseases. In conclusion, the study presents a novel therapeutic approach for OA, NE:TUB1-MNPs, leveraging the synergistic effects of peptide-functionalized nanoemulsions and magnetic nanoparticles to improve targeted delivery and therapeutic outcomes. This innovative formulation could pave the way for new treatments for OA and other joint-related conditions, offering significant advancements in regenerative medicine.