Drug Delivery Using Cationic Exosomes To Treat Osteoarthritis
Tanvi Vinod Pathrikar, PhD’24, bioengineering, who worked in BioE Associate Professor Ambika Bajpayee’s lab, published “Cartilage-targeting Exosomes for Delivery of Receptor Antagonist of Interleukin-1 in Osteoarthritis treatment” in Osteoarthritis and Cartilage. The findings demonstrate drug delivery of interleukin-1 receptor antagonist (IL-1RA), a disease-modifying osteoarthritis (OA) drug, using cationic exosomes.
Objective
Exosomes are nanosized cell secreted vesicles naturally and involved in joint tissue crosstalk that hold promise as drug carriers. Their negatively charged lipid bilayer, however, results in electrostatic repulsion from the anionic cartilage matrix limiting their applications in tissue targeting and drug delivery. The cartilage targeting exosomes was engineered by reversing their net surface charge and using them for sustained delivery of interleukin-1 receptor antagonist (IL-1RA), a disease-modifying osteoarthritis (OA) drug that suffers from rapid joint clearance and poor cartilage uptake.
Design
Exosomes were surface modified by anchoring optimally charged cartilage targeting cationic motifs, Avidin (Av) and arginine-rich cationic peptide carrier (CPC). IL-1RA was surface anchored and encapsulated within the exosomes, creating two formulations: ExoAv-IL-1RA and ExoCPC-IL-1RA. Their penetration and retention in healthy and early OA cartilage were evaluated and compared with unmodified exosomes. Efficacy of ExoAv-IL-1RA and ExoCPC-IL-1RA in suppressing IL-1-induced tissue catabolism was tested using IL-1α challenged bovine cartilage explants over an 8-day culture period with a single dose and compared with free IL-1RA.
Results
ExoAv-IL-1RA and ExoCPC-IL-1RA, penetrated and retained in the full-thickness of early-stage arthritic cartilage explants. Free IL-1RA failed to suppress IL-1α-induced catabolism over the culture period. In contrast, ExoCPC-IL-1RA significantly suppressed cytokine-induced GAG loss and nitrite release, enhancing cell metabolism and viability with only a one-time dose.
Conclusion
Cartilage targeting charge-reversed CPC anchored exosomes successfully targeted and delivered IL-1RA to early-stage arthritic cartilage. They hold promise as a cell-free, intra-cartilage, depot-forming carrier for sustained delivery of OA biologics.
