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Improved Reversion of Calcifications in Porcine Aortic Heart Valves Using Elastin-Targeted Nanoparticles.
Feldmann, Anja; Nitschke, Yvonne; Linß, Franziska; Mulac, Dennis; Stücker, Sina; Bertrand, Jessica; Buers, Insa; Langer, Klaus; Rutsch, Frank.
Affiliation
  • Feldmann A; Department of General Pediatrics, Muenster University Children's Hospital, D-48149 Muenster, Germany.
  • Nitschke Y; International Network of Ectopic Calcification (INTEC), 9000 Ghent, Belgium.
  • Linß F; Department of General Pediatrics, Muenster University Children's Hospital, D-48149 Muenster, Germany.
  • Mulac D; International Network of Ectopic Calcification (INTEC), 9000 Ghent, Belgium.
  • Stücker S; International Network of Ectopic Calcification (INTEC), 9000 Ghent, Belgium.
  • Bertrand J; Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, D-48149 Muenster, Germany.
  • Buers I; Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, D-48149 Muenster, Germany.
  • Langer K; International Network of Ectopic Calcification (INTEC), 9000 Ghent, Belgium.
  • Rutsch F; Department of Orthopaedic Surgery, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany.
Int J Mol Sci ; 24(22)2023 Nov 17.
Article in En | MEDLINE | ID: mdl-38003660
Calcified aortic valve disease in its final stage leads to aortic valve stenosis, limiting cardiac function. To date, surgical intervention is the only option for treating calcific aortic valve stenosis. This study combined controlled drug delivery by nanoparticles (NPs) and active targeting by antibody conjugation. The chelating agent diethylenetriaminepentaacetic acid (DTPA) was covalently bound to human serum albumin (HSA)-based NP, and the NP surface was modified using conjugating antibodies (anti-elastin or isotype IgG control). Calcification was induced ex vivo in porcine aortic valves by preincubation in an osteogenic medium containing 2.5 mM sodium phosphate for five days. Valve calcifications mainly consisted of basic calcium phosphate crystals. Calcifications were effectively resolved by adding 1-5 mg DTPA/mL medium. Incubation with pure DTPA, however, was associated with a loss of cellular viability. Reversal of calcifications was also achieved with DTPA-coupled anti-elastin-targeted NPs containing 1 mg DTPA equivalent. The addition of these NPs to the conditioned media resulted in significant regression of the valve calcifications compared to that in the IgG-NP control without affecting cellular viability. These results represent a step further toward the development of targeted nanoparticular formulations to dissolve aortic valve calcifications.
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Full text: 1 Database: MEDLINE Main subject: Aortic Valve Stenosis / Nanoparticles Language: En Journal: Int J Mol Sci Year: 2023 Type: Article Affiliation country: Germany

Full text: 1 Database: MEDLINE Main subject: Aortic Valve Stenosis / Nanoparticles Language: En Journal: Int J Mol Sci Year: 2023 Type: Article Affiliation country: Germany