Pulmonary Surfactant as a Vehicle for Intratracheal Delivery of Technetium Sulfur Colloid and Pentamidine in Hamster Lungs

Abstract

Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs. In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5). Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline. After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base. Autoradiographs were examined to evaluate 99mTc distribution. The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02). Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity. Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry. We calculated the fraction of each lung slice with detectable radioactivity. The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02). The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity. There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47). We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread.

Impact of formulation and methods of pulmonary delivery on absorption of parathyroid hormone (1–34) from rat lungs

“…The use of natural lung surfactant as a drug vehicle for pulmonary administration has been shown to allow deeper and more uniform deposition of instillates within the lungs. 31 However, no modification to overall deposition of the PTH solution was observed when incorporating pure DPPC in the instillate (Figs. 2-4).…”

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

“…It has been repeatedly shown that intratracheal surfactant administration results in better pulmonary distribution than aerosol and saline administration (28,29). Exogenous surfactant has been shown to enhance the pulmonary delivery and bioavailability of other potential therapeutic agents such as antioxidants, antibiotics, corticosteroids, and adenoviral vectors (8,30).…”

Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits

“…Exogenous surfactants have also been used to treat other lung disorders such as RDS in mature newborns and adult patients, the meconium aspiration syndrome and pneumonia [4][5][6][7][8][9]. Apart from its ability to lower surface tension, surfactant can also be used as a spreading agent [10][11][12][13].…”