Water soluble polymer films for intravascular drug delivery of antithrombotic biomolecules

Abstract

Over the past 10 years, the number of percutaneous coronary intervention (PCI) procedures performed in the United States has increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, remains a complication of this procedure. To traverse the complications associated with PCI, the investigation of therapeutic delivery has become an integral topic in modern research. One such therapeutic, a mimic of the proteoglycan decorin, termed DS-SILY, can mask exposed collagen and thereby effectively decrease platelet activation, has recently been developed by our lab. Drawing inspiration from coating technologies developed by the pharmaceutical industry, a fast-dissolving polymer film has been developed to deliver active therapeutic agents from a balloon catheter during PCI. This research investigates the release of DS-SILY from fast-dissolving polymer films composed of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG). Thin, uniform polymer films were produced via spin coating technique. The dissolution speed of the polymer films was found to be dependent on the concentration of polymer solution, where at least 65% of the films were shown to dissolve into nanometer sized polymer fragments within two minutes. DS-SILY, up to 6.26 μg/cm2, was loaded into the films and functional release of the mimic was demonstrated by its successful binding to collagen upon release. Furthermore, DS-SILY released from films resulted in increased platelet inhibition. These results indicate that use of fast-dissolving polymer films allow for the successful release of biomolecules and further investigation of their use for localized drug delivery during PCI procedures is warranted.

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

“…The cumulative percentage of drug released after 10 min (Q 10min ) was evaluated among different films. The drug dissolution from all formulae decreased as the concentration of the polymer increased, this expected result was in agreement with the data reported in the literature for fast dissolving oral films (Scott et al, 2013).…”

Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides

“…The conjugated molecule competitively binds to the platelet binding sites, which reduces the potential for thrombosis [37]. DS-SILY has been shown to inhibit platelet accumulation and matrix metalloproteinase (MMP)-mediated collagen degradation as well as to reduce the effects of pro-inflammatory and pro-fibrotic factors, platelet-derived growth factor (PDGF) and interferon-γ (IFN-γ), which typically activate smooth muscle cell proliferation and migration to cause intimal hyperplasia [35,37,38,39,40].…”

Formulation Optimization and <i>in Vitro</i> Characterization of Orally Disintegrating Films Using a Factorial Design and Mathematical Modeling for Drug Release

“…7,8) Numerous types of hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC), pullulan, maltodextrin, polyvinyl alcohol (PVA), and PVA-polyethylene glycol (PEG)-graft-copolymer have been widely studied due to their high chemical stability, biocompatibility, and low toxicity. [9][10][11][12][13][14][15][16][17] Generally, the polymer concentration used in preparing ODFs is around 45% w/w; it can increase up to 60-65% (w/w) in order to attain films with the desired quality attributes and characteristics. The concentration of plasticizer usually ranges from 0 to 20% (w/w).…”