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.
Hitzman
Cory J
CJ
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Elmquist
William F
WF
Wattenberg
Lee W
LW
Wiedmann
Timothy S
TS
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