Semi-fluorinated alkanes as carriers for drug targeting in acute respiratory failure

Abstract

Partial liquid ventilation (PLV) with perfluorocarbons may cause pulmonary recruitment in acute lung injury (ALI). Semi-fluorinated alkanes (SFAs) provide biochemical properties similar to perfluorocarbons. Additionally, SFAs are characterized by increased lipophilicity. Therefore, SFA-PLV may be considered for deposition of certain therapeutic drugs into atelectatic lung areas. In this experimental study SFA-PLV was evaluated to demonstrate feasibility, pulmonary recruitment, and efficacy of drug deposition. Feasibility of SFA-PLV was determined in pigs with and without experimental ALI. Animals were randomized to PLV with SFAs up to a cumulative amount of 30 mL x kg⁻¹ or to conventional mechanical ventilation. Pulmonary recruitment effects were determined by analyzing ventilation-perfusion distributions. Efficacy of intrapulmonary drug deposition was evaluated in further experiments by measuring drug serum concentrations in the course of PLV with SFA-dissolved α-tocopherol and ibuprofen. Increasing SFA doses caused progressive reduction of intrapulmonary shunt in animals with ALI, indicating pulmonary recruitment. PLV with SFA-dissolved α-tocopherol had no effect on serum levels of α-tocopherol, whereas PLV with SFA-dissolved ibuprofen caused a rapid increase of serum levels of ibuprofen. The authors conclude that SFA-PLV is feasible and causes pulmonary recruitment in ALI. Effectiveness of drug deposition in the lung obviously depends on the partitioning drugs out of the SFA phase into blood.

Semifluorinated Alkanes as New Drug Carriers—An Overview of Potential Medical and Clinical Applications

“…Basically, at this point, all studies evaluating SFAs as drug-delivery carriers confirmed that SFAs could be used as drug carriers in future lung applications [11,25,26,112].…”

“…Dembinski et al were the first research group to report PLV with SFA [11]. This study demonstrates the feasibility of PLV with the SFA perfluorohexyloctane (F6H8) in an (animal) experimental model of ALI and evaluates lung recruitment effects as a function of the SFA dose used.…”

“…The latter can hardly be reached by a conventional aerosol [112]. It has already been shown in liquid ventilation that both PFCs and SFAs can reduce alveolar surface tension, remove alveolar exudates from dependent lung regions and allow gas exchange [11,113]. A recent study hypothesized that an aerosol with these properties could significantly increase the likelihood of effective transport and deposition of drugs in the dependent regions of the ARDS lung [112].…”

“…SFAs are considered extremely hydrophobic, physically, chemically, physiologically inert, colorless, laser stable and, in comparison to PFCs, depict reduced densities-between 1.1 and 1.7 g/cm 3 [8,9]. The oxygen solubility of 40 to 50 vol% (water: 3 vol%) also makes SFAs potential candidates for the synthesis of blood substitutes [8,10] and for liquid ventilation [11], but also potential candidates for organ preservation [12].…”

“…This makes SFAs potentially interesting as new excipients, especially as (co-) solvents or to be used as drugdelivery systems [21,23,24]. They were evaluated as drug carriers in liquid ventilation [11], as aerosol [25,26] or intravenously [27], but also for topical use in the eye [28] or on the skin [29,30].…”