Engineering alginate microparticles for optimized accumulation in fetal rat myelomeningocele

Intraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect. We hypothesized that when the particle's surface charge was decreased and delivery concentration increased, particles would bind to the MMC defect more frequently and more specifically.

Alginate microparticles underwent surface modification to alter the particle charge. Dye-loaded alginate, alginate- dextran sulfate, and alginate- chitosan were injected on e17 into the amnion of a rat model of MMC and the incidence of successful binding and specificity of particle binding to the MMC defect were calculated. Specificity of binding was described using a defect-to-skin brightness ratio based on specimen imaging. Comparisons were made with chi-square, p< 0.05 marked significance.

There was no difference in the incidence of successful binding at e17 with 0.6 mg/fetal kg between the three tested alginate particles. However, alginate- dextran sulfate bound most specifically to the defect (p< 0.05). Alginate-dextran sulfate also demonstrated more frequent binding at higher doses than lower doses (79% at 1.2 mg/kg vs 38% at 0.6 mg/kg and 24% at 0.8 mg/kg, p< 0.01 for both). Specificity was not sacrificed at higher dose injections: defect-to-skin brightness ratio of 5.4 at 1.2 mg/kg vs 1.8 at 0.6 mg/kg (p< 0.05) CONCLUSION: We demonstrate that the intraamniotic injection of alginate-dextran sulfate microparticles at high concentration bind more frequently and more specifically to MMC defects than the previously tested unmodified alginate microparticles.