Description:
- Treatment for organ rejection and autoimmune diseases
- Drug carrier
Abstract
USC researchers have developed a novel strategy to carry CsA by binding it to its cognate receptor, cyclophilin. Significantly improved pharmacokinetic (PK) profile and therefore reduced systemic side effect were achieved by fusing cyclophilin with different types of elastin-like polypeptides (ELPs) utilizing recombinant protein-engineering. ELPs have a unique transition behavior where they self-assemble into coacervation in a fully temperature-dependent reversible manner, enabling easy purification and tunable PK behavior. Preliminary data also suggests that the ELP fusions stabilize other proteins and have the potential utility as drug carriers beyond CsA.
Benefit
- Fusion proteins effectively solubilize hydrophobic small-molecule drugs
- Reversibility of ELP phase separation can be precisely controlled by adjusting their structural properties?
- ELPs are biodegradable and low-immunogenic?
- Novel method for an effective drug delivery system?
Market Application
CyclosporinA (CsA) is a potent immunosuppressant that blocks T-cell proliferation and inhibits the release of inflammatory cytokines. It is used to prevent organ transplantation rejection and treat autoimmune diseases like rheumatoid arthritis and psoriasis. However, CsA has poor solubility, poor bioavailability, and induces serious adverse drug reactions such as nephrotoxicity and neurotoxicity. To overcome these limitations, new formulations for CsA are necessary to ensure successful delivery of this important immunosuppressant.
Publications
A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a mouse model of Sjv?gren s syndrome, J Control Release, 2018
Other
- Constructed ELP CsA carriers
- Tested in vitro and in vivo in mice
- Available for exclusive and non-exclusive license
Status: Patents issued, 11,464,867, 12,458,704