Technosphere insulin: defining the role of Technosphere particles at the cellular level.
BACKGROUND
Technosphere Insulin (TI) is a novel inhalation powder for the treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an ultra rapid pharmacokinetic profile that is distinctly different from all other insulin products but similar to natural insulin release. Such rapid absorption is often associated with penetration enhancers that disrupt cellular integrity.


METHODS
Technosphere Insulin was compared to a panel of known penetration enhancers in vitro using the Calu-3 lung cell line to investigate the effects of TI on insulin transport.


RESULTS
Measures of tight junction integrity such as transepithelial electrical resistance, Lucifer yellow permeability, and F-actin staining patterns were all unaffected by TI. Cell viability and plasma membrane integrity were also not affected by TI. In contrast, cells treated with comparable (or lower) concentrations of penetration enhancers showed elevated Lucifer yellow permeability, disruption of the F-actin network, reduced cell viability, and compromised plasma membranes.


CONCLUSIONS
These results demonstrate that TI is not cytotoxic in an in vitro human lung cell model and does not function as a penetration enhancer. Furthermore, TI does not appear to affect the transport of insulin across cellular barriers.
MannKind Corporation, Danbury, CT 06810, USA.
Robert
R
Angelo
Kathleen
K
Rousseau
Marshall
M
Grant
Andrea
A
Leone-Bay
Peter
P
Richardson
D000280:Administration, Inhalation; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D003652:Decanoic Acids / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D005650:Fumarates / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017830:Octoxynol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011208:Powders / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology
D003652:Decanoic Acids; D005650:Fumarates; D007328:Insulin; D010879:Piperazines; D011208:Powders; D003840:Deoxycholic Acid; C031071:decanoic acid; D017830:Octoxynol; C413290:3,6-bis(N-fumaryl-N(n-butyl)amino)-2,5-diketopiperazine