Tunable Protein Release from Acetalated Dextran Microparticles: A Platform for Delivery of Protein Therapeutics to the Heart Post-MI

The leading cause of death in the United States is cardiovascular disease. The majority of these cases result from heart failure post-myocardial infarction (MI). We present data providing evidence for use of acetalated dextran (AcDex) microparticles as a delivery vehicle for therapeutics to the hear...

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Bibliographic Details
Published in:Biomacromolecules 2013-11, Vol.14 (11), p.3927-3935
Main Authors: Suarez, Sophia, Grover, Gregory N, Braden, Rebecca L, Christman, Karen L, Almutairi, Adah
Format: Article
Language:English
Subjects:
Animals
Applied sciences
Biological and medical sciences
Dextrans - administration & dosage
Dextrans - pharmacokinetics
Drug Delivery Systems
Exact sciences and technology
Female
Fibroblast Growth Factor 2 - administration & dosage
General pharmacology
Humans
Hydrogen-Ion Concentration
Medical sciences
Molecular Structure
Myocardial Infarction - therapy
Myoglobin - administration & dosage
Myoglobin - chemistry
Natural polymers
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Rats
Rats, Sprague-Dawley
Starch and polysaccharides
Surface Properties
Time Factors
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Summary:The leading cause of death in the United States is cardiovascular disease. The majority of these cases result from heart failure post-myocardial infarction (MI). We present data providing evidence for use of acetalated dextran (AcDex) microparticles as a delivery vehicle for therapeutics to the heart post-MI. We harnessed the tunable degradation and acid-sensitivity of AcDex in the design of microparticles for intramyocardial injection. The particles released a model protein, myoglobin, and a sensitive growth factor, basic fibroblast growth factor (bFGF), over a wide range of time frames (from days to weeks) based on the percentage of cyclic acetals in the AcDex, which was easily controlled with acetalation reaction time. The release was shown in low pH environments, similar to what is found in an infarcted heart. bFGF maintained activity after release from the microparticles. Finally, biocompatibility of the microparticles was assessed.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm401050j