title: Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects.
abstract: OBJECTIVE
  Elastin-specific medial arterial calcification (MAC) is an arterial disease commonly referred as Monckeberg's sclerosis. It causes significant arterial stiffness, and as yet, no clinical therapy exists to prevent or reverse it. We developed albumin nanoparticles (NPs) loaded with disodium ethylene diaminetetraacetic acid (EDTA) that were designed to target calcified elastic lamina when administrated by intravenous injection.
  
  
  RESULTS
  We optimized NP size, charge, and EDTA-loading efficiency (150-200 nm, zeta potential of -22.89--31.72 mV, loading efficiency for EDTA~20%) for in vivo targeting in rats. These NPs released EDTA slowly for up to 5 days. In both ex-vivo study and in vivo study with injury-induced local abdominal aortic calcification, we showed that elastin antibody-coated and EDTA-loaded albumin NPs targeted the damaged elastic lamina while sparing healthy artery. Intravenous NP injections reversed elastin-specific MAC in rats after four injections over a 2-week period. EDTA-loaded albumin NPs did not cause the side effects observed in EDTA injection alone, such as decrease in serum calcium (Ca), increase in urine Ca, or toxicity to kidney. There was no bone loss in any treated groups.
  
  
  CONCLUSIONS
  We demonstrate that elastin antibody-coated and EDTA-loaded albumin NPs might be a promising nanoparticle therapy to reverse elastin-specific MAC and circumvent side effects associated with systemic EDTA chelation therapy.
authors.affiliation: Department of Bioengineering, Clemson University, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Bioengineering, Clemson University, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Nosoudi
authors.affiliation: Department of Bioengineering, Clemson University, USA. Electronic address: narenv@clemson.edu.
authors.forename: Naren
authors.initials: N
authors.lastname: Vyavahare
mesh_terms: D000368:Aged; D000418:Albumins / Q000737:chemistry; D000818:Animals; D002114:Calcinosis / Q000188:drug therapy* / Q000473:pathology; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000009:adverse effects / Q000379:methods*; D016503:Drug Delivery Systems; D004492:Edetic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D051381:Rats; D013552:Swine
chemical_list: D000418:Albumins; D002614:Chelating Agents; D004492:Edetic Acid
keywords: Albumin nanoparticles; Arteriosclerosis; Elastin antibody; Medial calcification; Targeted EDTA chelation therapy