Pulmonary delivery of deslorelin: large-porous PLGA particles and HPbetaCD complexes.
OBJECTIVE
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.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Kavitha
K
Koushik
Devender S
DS
Dhanda
Narayan P S
NP
Cheruvu
Uday B
UB
Kompella
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004337:Drug Carriers; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D019999:Pharmaceutical Solutions; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D017329:Triptorelin Pamoate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D019999:Pharmaceutical Solutions; D011108:Polymers; D011208:Powders; D047392:beta-Cyclodextrins; D017329:Triptorelin Pamoate; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C066438:deslorelin