Development of a Respirable, Sustained Release Microcarrier for 5-Fluorouracil I: In Vitro Assessment of Liposomes, Microspheres, and Lipid Coated Nanoparticles

The release rate of 5-fluorouracil (5-FU) from liposomes, microspheres, and lipid-coated nanoparticles (LNPs) was determined by microdialysis to investigate their use as a respirable delivery system for adjuvant (postsurgery) therapy of lung cancer. 5-FU was incorporated into liposomes using thin film hydration and into microspheres and LNPs by spray drying. Primary particle size distributions were measured by dynamic light scattering. Liposomes released 5-FU in 4–10h (k1=0.44–2.31/h, first-order release model). Extruded vesicles with diameters less than one micron released 5-FU more quickly than nonextruded vesicles. With poly-(lactide) (PLA) and Poly-(lactide-co-glycolide) (PLGA) microspheres, slower release rates were observed (k1=0.067–0.202/h). Increasing the lactide:glycolide ratio (50:50–100:0) resulted in a progressive decrease in the release rate of 5-FU. poly-(lactide-co-caprolactone) (PLCL) microspheres released 5-FU more rapidly compared to PLGA systems (k1=0.254–0.259/h). LNPs formulated with polymeric core excipients had lower release rates compared to monomeric excipients (k1=0.043–0.105/h vs. k1=0.192–0.345/h). Changing the lipid chain length of the shell lipid components had a relatively minor effect (k1=0.043–0.129/h). Overall, these systems yielded a wide range of delivery durations that may be suitable for use as an inhalation delivery system for adjuvant therapy of lung cancer.