Anti-inflammatory loaded poly-lactic glycolic acid nanoparticle formulations to enhance myocardial gene transfer: an in-vitro assessment of a drug/gene combination therapeutic approach for direct injection.

BACKGROUND: Cardiac gene therapy for heart disease is a major translational research area with potential, yet problems with safe and efficient gene transfer into cardiac muscle remain unresolved. Existing methodology to increase vector uptake include modifying the viral vector, non-viral particle encapsulation and or delivery with device systems. These advanced methods have made improvements, however fail to address the key problem of inflammation in the myocardium, which is known to reduce vector uptake and contribute to immunogenic adverse events. Here we propose an alternative method to co-deliver anti-inflammatory drugs in a controlled release polymer with gene product to improve therapeutic effects. METHODS: A robust, double emulsion production process was developed to encapsulate drugs into nanoparticles. Briefly in this proof of concept study, aspirin and prednisolone anti-inflammatory drugs were encapsulated in various poly-lactic glycolic acid polymer (PLGA) formulations. The resultant particle systems were characterized, co-delivered with GFP plasmid, and evaluated in harvested myocytes in culture for uptake. RESULTS: High quality nanoparticles were harvested from multiple production runs, with an average 64 ± 10 mg yield. Four distinct particle drug system combinations were characterized and evaluated in vitro: PLGA(50:50) Aspirin, PLGA(65:35) Prednisolone, PLGA(65:35) Aspirin and PLGA(50:50) Prednisolone Particles consisted of spherical shape with a narrow size distribution 265 ± 104 nm as found in scanning electron microscopy imaging. Prednisolone particles regardless of PLGA type were found on average ≈ 100 nm smaller than the aspirin types. All four groups demonstrated high zeta potential stability and re-constitution testing prior to in vitro. In vitro results demonstrated co uptake of GFP plasmid (green) and drug loaded particles (red) in culture with no incidence of toxicity. CONCLUSIONS: Nano formulated anti-inflammatories in combination with standalone gene product therapy may offer a clinical solution to maximize cardiac gene therapy product effects while minimizing the risk of the host response in the inflammatory myocardial environment.

Early Surgical Reconstruction of Sternum with Longitudinal Rigid Polymer Plating after Acute Chest Trauma.

PURPOSE: The surgical management of the patients with traumatic sternal fractures remains controversial. The aim of this study was to evaluate the effectiveness of an early surgical reconstruction of a displaced sternal fracture utilizing longitudinal rigid polymer fixation in the settings of an acute chest trauma. METHODS: To perform the sternal fixation, we utilized a longitudinal rigid plating system. The plate is made of polyether ether ketone (PEEK), an organic thermoplastic polymer. RESULTS: We used the entire length of the plate on each side of the fracture, secured in multiple places with 6-8 screws. Once the plates have been fully secured we tighten all the screws with a screwdriver. We demonstrated that the method minimizes pain and prevents the development of pulmonary complications. CONCLUSION: This technique provides cosmetically acceptable results, minimizing risk of sternal nonunion, and decreases length of hospitalization.