Recently, there has been growing interest towards utilization of non-spherical carriers in targeted delivery applications. The current methods developed for rod fabrication have expensive/complicated setups with low production rates. An emulsion solvent evaporation (ESE) method has been recently described as a very simple and scalable alternate method, where rods are fabricated by stretching the emulsion droplets with shear. However, this technique has been unable to produce rods in the size range applicable for <i>in vivo </i>use due to the risk of embolism.<br/><br/>Here, we have modified the ESE technique to a two-step fabrication method where the droplet formation and emulsification steps are separated to achieve smaller sized rods. The size of the droplet is fixed in the first, emulsification, step, and the stretching of the initially formed droplets is achieved by a step change in the viscosity of our system. With this system, we were able to scale down the size of the poly(lactic co-glycolic acid), PLGA, rods fabricated with the ESE technique down to major axis sizes of 3.5 µm and minor axis sizes of 700 nm while maintaining the rod fabrication yield at 70% or higher. Furthermore, we find that the choice of our oil phase solvent and surface-active molecule determines the rod fabrication yield. A switch to chloroform from the previously used dichloromethane significantly increased particle yield due to its slower evaporation rate, giving more time to the droplets to be stretched. Similarly, of the three surface active molecules evaluated, trizma base, sodium tripolyphosphate and sodium metaphosphate, sodium metaphosphate gave the highest rod fabrication yield due to having stronger interactions with the hydrophilic groups of the biodegradable polymer in the oil phase, which then significantly decreasing the interfacial tension in the system. We demonstrated the capability of our two-step method to fabricate rods loaded with therapeutics and contrast agents via loading of the Nile Red fluorescent dye. In conclusion, our work has introduced a simple method for fabricating non-spherical carriers in a range of sizes for targeted delivery applications.

Modified two-step emulsion solvent evaporation technique for fabricating biodegradable rod-shaped drug carriers

254th National Meeting (2017)

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