Development of a respirable, sustained release microcarrier for 5-fluorouracil I: In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles

Cory J. Hitzman, William F. Elmquist, Lee W. Wattenberg, Timothy S. Wiedmann

Research output: Contribution to journalComment/debatepeer-review

95 Scopus citations

Abstract

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 (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 (k 1 = 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.

Original languageEnglish (US)
Pages (from-to)1114-1126
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume95
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • 5-fluorouracil
  • Lipid-coated nanoparticles
  • Liposomes
  • Lipospheres
  • Lung cancer
  • Microspheres
  • Sustained release

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