title: Comparing the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.
abstract: BACKGROUND
  The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.
  
  
  METHODS
  Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption.
  
  
  RESULTS
  Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively.
  
  
  CONCLUSIONS
  Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.
authors.affiliation: Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Xu
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Fu
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000042:Absorption; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006865:Hydrogenation; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D007327:Insufflation; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D008081:Liposomes; D008297:Male; D045423:Microbubbles; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism*; D018675:Toxicity Tests
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines