Bacterial sensitivity assessment of multifunctional polymeric coatings for airway stents.

Current interventional technology for pediatric airway obstruction consists of cardiovascular stents and silicon tubes. These devices are composed of permanent materials that have limitations in biocompatibility and mechanical properties that make them controversial for used in pediatrics. Bioresorbable stents offer a temporary intervention that dissolves in the body over time and can serve as a platform for local drug delivery. Here we investigate a novel approach to use an antibiotic, ciprofloxacin, as a polymerization initiator to synthesize poly(ciprofloxacin fumaric acid) (PCFA) and then a second polymer using gadodiamide as an initiator to synthesize poly(gadodiamide ciprofloxacin fumaric acid) (PGCFA). Polymer structure, degradation, thermal properties, and rheological behavior were analyzed. Ciprofloxacin released was determined and polymer degradation extracts were used in bacterial sensitivity assessments with four common airway pathogens. PCFA and PGCFA polymers and drug release properties were compared to our previously published polymer poly(fumaric acid) (PFA). These novel polymers enable new possibilities as coatings for bioresorbable biomedical applications that require antibiotic resistance and imaging capabilities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2153-2161, 2017.

Thermally processed polymeric microparticles for year-long delivery of dexamethasone.

Dexamethasone-releasing poly(lactic-co-glycolic acid) (PLGA) microparticles were formulated using a solvent displacement technique with the addition of distillation aiming to increase drug delivery lifetime. Two PLGA copolymer ratios (50:50 and 75:25) were used to determine the influence of lactic acid and glycolic acid ratio on microparticle characteristics. The addition of distillation significantly slows the release of dexamethasone compared to traditional solvent removal via evaporation while still maintaining a therapeutic dosage. Microparticles formulated with PLGA 50:50 controllably release dexamethasone up to one year and 75:25 release up to two years in-vitro. The ratio of lactic acid to glycolic acid plays a significant role in microparticle stability, drug loading efficiency, and thermal properties. In all, this formulation technique offers new prospects for inflammation suppression in pediatric vascular and airway diseases.

Novel bioresorbable stent coating for drug release in congenital heart disease applications.

A novel double opposed helical poly-l-lactic acid (PLLA) bioresorbable stent has been designed for use in pediatrics. The aim was to test the PLLA stent biocompatibility. The PLLA stent was immersed into whole pig's blood in a closed loop circuit then fibrin and platelet association was assessed via enzyme-linked immunosorbent assay. D-Dimer was valued at 0.2 ± 0.002 ng/mL and P-selectin 0.43 ± 00.01 ng/mL indicating limited association of fibrin and platelets on the stent. To improve biocompatibility by targeting inflammatory cells, dexamethasone was incorporated on PLLA fibers with two coating methods. Both coatings were poly(l-lactide-co-glycolide) acid (PLGA) but one was made porous with sucrose while the other remained nonporous. There was no change in mechanical properties of the fiber with either coating of PLGA polymer. The total amount of dexamethasone released was then determined for each coating. The cumulative drug release for the porous fiber was significantly higher (∼100%) over 8 weeks than the nonporous fiber (40%). Surface examination of the fiber with scanning electron microscopy showed more surface microfracturing in coatings that contain pores. The biocompatibility of this novel stent was demonstrated. Mechanical properties of the fiber were not altered by coating with PLGA polymer. Anti-inflammatory drug release was optimized using a porous PLGA polymer.

Poly(gadodiamide fumaric acid): A Bioresorbable, Radiopaque, and MRI-Visible Polymer for Biomedical Applications.

Bioresorbable medical devices once implanted into the body are "invisible" to imaging techniques such as X-ray/fluoroscopy and magnetic resonance imagining (MRI). Prior attempts to produce radiopaque polymers have limited success due to their inability to generate homogeneous mixtures of polymer and contrast agent without subsequent alterations in polymer structure. Here we investigate a novel approach in which a MRI contrast medium, gadodiamide, can be used as a polymerization initiator in poly(propylene fumarate) (PPF) synthesis to achieve a radiopaque and MRI-visible polymer poly(gadodiamide fumaric acid) (PGFA). With this method polymer structure, thermal properties, and rheological behavior are conserved with no prior manipulation to monomer units necessary. This unique polymer in combination with poly(lactic-co-glycolic acid) (PLGA) can be formulated into MRI-visible nanoparticles with drug delivery potential. This novel polymer in both liquid and nanoparticle form enables new possibilities in medical device and drug delivery design.