title: Phospholipid-induced in vivo particle migration to enhance pulmonary deposition.
abstract: Amount of drug actually reaching the target region in the lung following pulmonary inhalation is often estimated at less than 10% for older devices. Current particle and device engineering technologies have improved on this but still fail to recover the "wasted" fraction of the drug and deliver it deeper into the lungs, which is generally desirable. FDA has approved several exogenous surfactants for prophylaxis and rescue treatment of respiratory distress syndrome (RDS). Their approved mode of administration (intratracheal instillation) and site of action (alveolar spaces) suggest that the phospholipids in the exogenous surfactants can spread from the trachea to alveolar air spaces and exert advantageous effects. We investigated whether in vivo lung migration of particles based on this phenomenon was possible and could be quantified based on changes in total and regional deposition of fluorescently labeled latex beads, utilized as an insoluble drug model. Following intranasal administration of beads, migration to rodent lungs was monitored upon intranasal instillation of Survanta (exogenous surfactant) or saline (control). After intranasal instillation approximately 12% of beads were found to migrate to the lung, and total lung deposition increased by approximately 10% on administration of Survanta or saline (control). After intranasal administration approximately 1% of beads in the lung were found to migrate to peripheral regions of the lungs, and a four- to six-fold increase in peripheral lung deposition was observed after Survanta instillation, compared to the saline control, which was determined to be independent of dose and volume of Survanta instillate in the range we studied. The in vivo rodent studies provided support for the idea that intranasally administered particles deposited in non-target lung locations may be translocated to peripheral sites in the lung therapeutically after surfactant application.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Maryland, USA. sudipta.ganguly@spcorp.com
authors.forename: Sudipta
authors.initials: S
authors.lastname: Ganguly
authors.forename: Vikas
authors.initials: V
authors.lastname: Moolchandani
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Roche
authors.forename: Paul S
authors.initials: PS
authors.lastname: Shapiro
authors.forename: Shailaja
authors.initials: S
authors.lastname: Somaraju
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Eddington
authors.forename: Richard N
authors.initials: RN
authors.lastname: Dalby
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D007840:Latex / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D001688:Biological Products; D007840:Latex; D010743:Phospholipids; C072197:beractant