Pulmonary delivery of deslorelin: large-porous PLGA particles and HPbetaCD complexes

Pharm Res. 2004 Jul;21(7):1119-26. doi: 10.1023/b:pham.0000032997.96823.88.


Purpose: To compare the systemic delivery of deslorelin following intratracheal administration of different deslorelin formulations. The formulations included dry powders of deslorelin, large-porous deslorelin-poly(lactide-co-glycolide) (PLGA) particles, and small conventional deslorelin-PLGA particles. Also, solution formulations of deslorelin and deslorelin-hydroxy-propyl-beta-cyclodextrin (HPbetaCD) complexes were tested.

Methods: Dry powders of deslorelin, large-porous (mean diameter, 13.8 microm; density, 0.082 g/cc), and small conventional (mean diameter, 2.2 microm; density, 0.7 g/cc) deslorelin-PLGA particles and solutions of deslorelin with or without HPbetaCD were administered intratracheally to Sprague-Dawley rats. Blood samples were collected at 3 h, 1, 3, and 7 days postdosing, and plasma deslorelin concentrations were determined using enzyme immunoassay. At the end of 7 days, lungs were isolated, and bronchoalveolar lavage fluid was collected and analyzed for deslorelin.

Results: At the end of 7 days, deslorelin plasma concentrations in the large-porous deslorelin-PLGA particle group were 120-fold and 2.5-fold higher compared to deslorelin powder and small conventional deslorelin-PLGA particles, respectively. Co-administration of HPbetaCD resulted in 2-, 3-, and 3-fold higher plasma deslorelin concentrations at 3 h, 1 and 3 days, respectively, compared to deslorelin solution. On day 7, deslorelin concentrations in bronchoalveolar lavage fluid as well as plasma were in the order: large porous particles > small conventional particles > deslorelin-HPbetaCD solution > deslorelin powder > deslorelin solution.

Conclusions: Large-porous deslorelin PLGA particles can sustain deslorelin delivery via the deep lungs. Co-administration of HPbetaCD enhances the systemic delivery of deslorelin. The pulmonary route is useful as a noninvasive alternative for the systemic delivery of deslorelin.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Inhalation
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Drug Carriers
  • Lactic Acid / chemistry*
  • Lung / metabolism*
  • Male
  • Particle Size
  • Pharmaceutical Solutions
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Porosity
  • Powders
  • Rats
  • Rats, Sprague-Dawley
  • Trachea
  • Triptorelin Pamoate / administration & dosage*
  • Triptorelin Pamoate / analogs & derivatives*
  • Triptorelin Pamoate / chemistry
  • Triptorelin Pamoate / pharmacokinetics
  • beta-Cyclodextrins / chemistry*


  • Drug Carriers
  • Pharmaceutical Solutions
  • Polymers
  • Powders
  • beta-Cyclodextrins
  • Triptorelin Pamoate
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • deslorelin