Methods for targeted delivery of agents to degraded elastic fibers

An in vivo method for delivery of a biologically active compound to a degraded elastic fiber embedded within a live, native, damaged connective tissue of a subject, the method comprising:

• directly or systemically providing a delivery agent to the damaged connective tissue of the subject, the damage including the degraded elastic fiber, the delivery agent having an average diameter of from about 50 nm to about 400 nm and a negative surface charge, the delivery agent comprising:
• a) a biodegradable particle, the biodegradable particle comprising a biocompatible polymer, the biodegradable particle being associated with the biologically active compound, the biologically active compound comprising a tannin, a flavonoid, a flavolignan, a phenolic rhizome, a favan-3-ol a cathepsins inhibitor, an MMP inhibitor, an elastase inhibitor, a lysyl oxidase, copper ions, forskolin, TGF-β, ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid, Nitrilotriacetic acid, hydroxyethyl ethylenediaminetriacetic acid, 8-Hydroxy-7-iodo-5-quinolinesulfonic acid, poly(gamma-glutamic acid), sodium thiosulphate, or alpha-lipoic acid,
• b) a molecular spacer bonded to a surface of the biodegradable particle at a first end of the molecular spacer, and
• c) an anti-elastin antibody or an elastin binding fragment thereof that has been modified to include thiol functionality, wherein the thiolated anti-elastin antibody or thiolated elastin binding fragment thereof is bonded to a second end of the molecular spacer via the thiol functionality and is present on the delivery agent at a concentration of from 1 microgram anti-elastin antibody or elastin binding fragment thereof per milligram delivery agent to 7.5 microgram anti-elastin antibody or elastin binding fragment thereof per milligram delivery agent;
• wherein
• following the step of providing the delivery agent to the subject, the delivery agent migrates to the damaged connective tissue and penetrates a medial layer of the damaged connective tissue, whereupon the anti-elastin antibody or elastin binding fragment thereof binds exposed elastin of the degraded elastic fiber and thereby binds the particle to the degraded elastic fiber embedded within the live, native, damaged connective tissue of the subject.