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 4-10 h (k(1) = 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 (k(1) = 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 (k(1) = 0.254-0.259/h). LNPs formulated with polymeric core excipients had lower release rates compared to monomeric excipients (k(1) = 0.043-0.105/h vs. k(1) = 0.192-0.345/h). Changing the lipid chain length of the shell lipid components had a relatively minor effect (k(1) = 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.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Cory J
CJ
Hitzman
William F
WF
Elmquist
Lee W
LW
Wattenberg
Timothy S
TS
Wiedmann
D000280:Administration, Inhalation; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D005612:Freeze Drying; D008081:Liposomes; D017551:Microdialysis; D008863:Microspheres; D049329:Nanostructures; D010316:Particle Size
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D008081:Liposomes; D005472:Fluorouracil