The preparation and application of pulmonary surfactant nanoparticles as absorption enhancers in insulin dry powder delivery.
OBJECTIVE
To study the preparation and application of pulmonary surfactant (PS) nanoparticles as absorption enhancers in insulin dry powder delivery. PS is a complex mixture of mainly phospholipids and proteins. The composition leads to a unique spreading effect of the surfactants as well as spontaneous nanoparticles formation, which may be favorable characteristics of pulmonary drug delivery systems.


METHODS
In this article, insulin has been a model drug, as an important drug in lowering blood glucose and as a classic protein drug. PS was extracted from pig lungs and was observed as nanoparticles morphology in water by transmission electron microscopy after preparation. Inhalation dry powders were formulated by PS nanoparticles, insulin, and other excipients. In addition, blood glucose level of rats was determined when the insulin dry powder of PS group and control group was delivered by inhalation route.


RESULTS
Compared with control group, scanning electron microscopy showed that the dry powders of PS group possess similar particle size and smoother surface. The spray-dried powders re-suspended possessed similar nanoparticle appearance compared with the original PS suspension. Animal studies showed that blood glucose level was effectively reduced when the insulin dry powder of PS group was delivered by inhalation route. Compared with subcutaneous injection group (4 U/kg), the relative pharmacological bioavailability of the insulin dry powders of control group (14 U/kg) and PS group (14 U/kg) was 19.97% and 32.57%, respectively.


CONCLUSIONS
PS nanoparticles, as absorption enhancers used in dry powder inhalation, could evidently enhance the effect of insulin in lowering blood glucose.
Zhang
Yong
Y
Department of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Zhu
Jiabi
J
Tang
Yue
Y
Chen
Xijing
X
Yang
Yan
Y
D000042:Absorption; D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D011208:Powders; D011663:Pulmonary Surfactants / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions; D013552:Swine
D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011208:Powders; D011663:Pulmonary Surfactants; D013535:Suspensions