(558b) Varying Formulation Methods to Achieve Desired Diameter of Poly(caprolactone) Nanoparticles and Microparticles to Treat Disease

Polymeric polymers show great promise for their sustained release profiles, tunable size, and loading. These drug delivery systems (DDS) decrease some of the delivery issues of pharmaceutics such as low solubility and low bioavailability. DDS can also be used to treat a variety of different diseases, requiring different routes of administration, ranging from allergic asthma to cancer. For example, allergic asthma is typically treated with inhaled aerosols where particles would need to be one to five micrometers in diameter to be aerodynamically favorable for lung deposition. On the other hand, cancer is typically treated intravenously requiring drastically smaller particles ranging in diameter from 100-300 nanometers to preferentially permeate solid tumors. Poly(caprolactone) (PCL) has been FDA approved for use in surgical implants, sutures, and long-term DDS. Drug release is mediated by diffusion, accelerated by polymer degradation. Poly-lactones degrade into monomer by hydrolysis, and PCL is favorable because it is considered biocompatible, biodegradable, and bioresorbable. However, PCL has not been widely used in nanoparticle and microparticle formulations because it has a very slow degradation time, particularly compared with other suitable polymers. The advantage to using PCL in this study is that PCL has been found to be highly tunable, with diffusion dominating short-term drug release, independently of the time it takes to fully degrade the polymer. Varying parameters in the double emulsion solvent evaporation method coupled with size separation, different monodisperse nanospheres and microspheres of PCL DDS were generated. Two solvents, dichloromethane (DCM) and chloroform (Chl); two different surfactants, polyvinyl alcohol and tween-80; and three molecular weights of PCL (25,000; 45,000; 80,000) were used to create the PCL particles. Additional parameters such as length of sonication, concentration of surfactant, ratio of PCL to solvent, and ratio of oil to water phase were varied to create different particle size distributions. Scanning Electron Microscopy (SEM) along with ImageJ quantified particle size and morphology. Overall, this method has generated particles as large as 3 micrometer and as small as 300 nanometers. These results indicate that we can generate particles suitable for both allergic asthma treatment, as well as cancer treatment. Preliminary in vitro studies have indicated that blank particles do not induce harmful side effects, supporting that the PCL is biocompatible. Together, these results indicate that varying emulsion properties is sufficient at generating DDS with a wide variety of potential applications, thus making this method suitable for advancing treatment in an array of diseases. To the best of our knowledge, this is the first such investigation utilizing PCL in tuning polymer properties.