Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect.
Insulin loaded PLGA nanospheres having weight mean diameters of 400 nm were prepared by the modified emulsion solvent diffusion method in water. The nanosphere recovery and the drug recovery in the nanospheres were 74.8%+/-4.71 and 46.8%+/-7.01, respectively. Eighty five percent of the drug was released from the nanospheres at the initial burst, followed by prolonged releasing of the remaining drug for a few hours in saline at 37 degrees C. The aqueous dispersions (6 mg/ml) of PLGA nanospheres were nebulized by a sieve type ultrasonic nebulizer to discrete droplets of 5 approximately 7 microm in mean diameters, 75% of which were successfully delivered into the alveolar fraction in a cascade impactor inhaled at 28.3 l/min. The nebulized PLGA nanospheres were administered via a spacer by using a constant volume respirator into the trachea of the fasted guinea pig for 20 min. After the administration of 3.9 I.U./kg insulin with the PLGA nanospheres, the blood glucose level was reduced significantly and the hypoglycemia was prolonged over 48 h, compared to the nebulized aqueous solution of insulin as a reference (6 h). This result could be attributed to the sustained releasing of insulin from the nanospheres deposited widely on to the whole of lung.
Kawashima
Y
Y
Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, Japan. yoshiaki@gifu-pu.ac.jp
Yamamoto
H
H
Takeuchi
H
H
Fujioka
S
S
Hino
T
T
D000280:Administration, Inhalation; D000818:Animals; D001672:Biocompatible Materials; D004337:Drug Carriers; D005070:Evans Blue; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D019344:Lactic Acid; D008168:Lung / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D009330:Nebulizers and Vaporizers; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013997:Time Factors
D001672:Biocompatible Materials; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005070:Evans Blue