N,N,N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: Interaction with a model pulmonary surfactant

N,N,N-Trimethyl chitosan (TMC), a biocompatible and biodegradable derivative of chitosan, is currently used as a permeation enhancer to increase the translocation of drugs to the bloodstream in the lungs. This article dis-cusses the effect of TMC on a mimetic pulmonary surfactant, Curosurf (R), a low-viscosity lipid formulation administered to preterm infants with acute respiratory distress syndrome. Curosurf (R) exhibits a strong interaction with TMC, resulting in the formation of aggregates at electrostatic charge stoichiometry. At nanoscale, Curosurf (R) undergoes a profound reorganization of its lipid vesicles in terms of size and lamellarity. The initial micron-sized vesicles (average size 4.8 mu m) give way to a froth-like network of unilamellar vesicles about 300 nm in size. Under such conditions, neutralization of the cationic charges by pulmonary surfactant may inhibit TMC permeation enhancer capacity, especially as electrostatic charge complexation is found at low TMC content. The permeation properties of pulmonary surfactant-neutralized TMC should then be evaluated for its applicability as a permeation enhancer for inhalation in the alveolar region.

Automated summary

This article discusses the effect of N,N,N-trimethyl chitosan (TMC) on a mimetic pulmonary surfactant, Curosurf (R). The results show that TMC has a strong interaction with Curosurf (R), leading to the formation of aggregates at electrostatic charge stoichiometry. At the nanoscale, Curosurf (R) undergoes a profound reorganization of its lipid vesicles in terms of size and lamellarity. The neutralization of cationic charges by pulmonary surfactant may inhibit the permeation enhancement capacity of TMC, especially at low TMC content. Therefore, the permeation properties of pulmonary surfactant-neutralized TMC should be evaluated for its applicability as a permeation enhancer for inhalation in the alveolar region.