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Creation of tPA conjugated dendrimer nanoparticles (780.4)
Author(s) -
Paliwal Vipin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.780.4
Subject(s) - dendrimer , carbodiimide , chemistry , conjugate , combinatorial chemistry , tissue plasminogen activator , polymer chemistry , biochemistry , mathematical analysis , mathematics
A drug delivery system was created using nanoparticles called dendrimers. Tissue plasminogen activator (tPA), a clot busting drug given to stroke patients was covalently bonded to dendrimers using surface active organic functional groups including carboxylic acids, amines, and alcohol. Methods included esterification using a heterobifunctional coupling agent EDC (1‐ethyl‐3[3‐dimethylaminpropyl]carbodiimide hydrochloride. A fourth generation dendrimer (hydroxyl‐terminated poly(amidoamine) PAMAM dendrimers (G4‐OH) with 64 binding sites was chosen to bind the human tPA protein molecule (molecular mass of 72 kDa). Several dilutions of dendrimer were tested to achieve the best drug‐nanoparticle stoichiometric ratio and avoid overcrowding. Upon completion of the synthesis the drug‐dendrimer conjugate was purified using centrifugal filtration. The tPA‐dendrimer complex was tested for clot dissolving activity using an in vitro Thrombin assay. It was concluded that Succinamic acid functionalized dendrimer at a 1:1 drug to nanoparticle ratio was found to have the highest clot dissolving activity when compared to control tPA standard. This tPA‐dendrimer conjugate could be more effective, quicker reacting than tPA drug alone and may find use in treating stroke, pulmonary embolism and heart attack patients. Grant Funding Source : National Science Foundation