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

Abstract

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 prototype trypan blue-containing PLGA millirods were fabricated under a compression pressure of 4.6 x 10(6) Pa and different fabrication temperatures for 2 h. The scanning electron microscopy results showed complete polymer annealing for millirods fabricated at 80 and 90 degrees C, while the cross sections of the 60 and 70 degrees 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 x 10(8) Pa, which provides sufficient stiffness for implantation within the tumor tissue. In addition, a Delta c(p) method was developed to determine the loading density of trypan blue in the PLGA millirods by differential scanning calorimetry. Results from the Delta c(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 degrees C, respectively. Millirods fabricated at 90 degrees 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.

Advances in image-guided Intratumoral Drug Delivery Techniques

“…Several biodegradable polymers such as polyanhydrides, polyesters and poly(orthoesters) are used to formulate these drug delivery devices. In particular, implants comprised of poly(lactic acid) (PLA), poly(glycolic acid) (PGA) or their copolymer poly(lactic-co-glycolic acid) (PLGA) are especially common [49,50]. The biocompatibility, degradation and drug-release mechanisms from PLGA matrices have been well established [51,52].…”

“…Another preformed implant device in the shape of a thin cylinder or ‘millirod’ formed by compression heat molding has been designed in particular for use with minimally invasive techniques and has been extensively studied. These implants are comprised of PLGA and have been developed as both sustained and dual release formulations [49,61]. Dual release millirods produce an initial burst of drug release to quickly reach therapeutic drug dosage, followed by sustained release to maintain drug levels (Figure 3).…”

Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants

“…Doxorubicin-containing millirods were fabricated by combining 65% poly(D,L-lactide-coglycolide) (PLGA) microspheres, 13.5% doxorubicin, and 21.5% NaCl (w/w) using a previously published compression-heat molding procedure [18]. The mixture was blended with a mortar and pestle, packed into a Teflon tube (1.6 mm outside diameter), and compressed with steel plungers (1.6 mm inside diameter) at 90°C for 2 hours.…”

New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect

“…A similar approach could be used to develop the smart RT biomaterial loaded with CNP. Alternatively, CNP can be incorporated in poly( d , l -lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production [31,32]. The results here provide impetus for more research to develop such next generation RT biomaterials.…”