Fabrication and characterization of controlled release poly(D,L-lactide-co-glycolide) millirods

A compression-heat molding procedure was developed to fabricate poly(D,L-lactide-co-glycolide) (PLGA) controlled release drug delivery devices for the local treatment of tumors. The drug delivery devices were designed in the shape of a cylindrical millirod (1.6-mm diameter, 10-mm length), which allows them to be implanted by a modified 14-gauge tissue biopsy needle into tumor tissues via image-guided interventional procedures. In this study, the proto-type trypan blue-containing PLGA millirods were fabricated under a compression pressure of 4.6 × 10⁶ Pa and different fabrication temperatures for 2 h. The scanning electron microscopy results showed complete polymer annealing for millirods fabricated at 80 and 90°C, while the cross sections of the 60 and 70°C millirods showed incompletely annealed PLGA microspheres and trypan blue powders. The density, flexural modulus, and release properties of the PLGA millirods were also characterized and compared. The average values of the density and flexural modulus of the millirods increased with an increase in fabrication temperature. The flexural modulus values of most PLGA millirods were above 1 × 10⁸ Pa, which provides sufficient stiffness for implantation within the tumor tissue. In addition, a Δc_p method was developed to determine the loading density of trypan blue in the PLGA millirods by differential scanning calorimetry. Results from the Δc_p measurement showed that trypan blue was homogeneously distributed in the millirod. Release studies in phosphate-buffered saline showed that the release rate decreased for the millirods fabricated at higher temperatures. The times for the release of 50% trypan blue were 5, 25, 25, and 25 h for millirods fabricated at 60, 70, 80, and 90°C, respectively. Millirods fabricated at 90°C had the most reproducible release profiles. The results from this study established compression-heat molding as an effective method to fabricate controlled release PLGA millirods with sufficient mechanical strength and reproducible release profiles for local cancer therapy.