Enhancing the Spreading Behavior on Pulmonary Mucus Mimicking Subphase via Catanionic Surfactant Solutions: Toward Effective Drug Delivery through the Lungs

Mol Pharm. 2018 Mar 5;15(3):1361-1370. doi: 10.1021/acs.molpharmaceut.8b00086. Epub 2018 Feb 20.


Effective and efficient spreading of drug formulations on the pulmonary mucosal layer is key to successful delivery of therapeutics through the lungs. The pulmonary mucus layer, which covers the airway surface, acts as a barrier against therapeutic agents, especially in the case of chronic lung diseases due to increased thickness and viscosity of the mucus. Therefore, spreading of the drug formulations on the airways gets harder. Although spreading experiments have been conducted with different types of formulations on mucus-mimicking subphases, a highly effective formulation is yet to be discovered. Adding surfactant to such formulations decreases the surface tension and triggers the Marangoni forces to enhance the spreading behavior. In this study, catanionic (cationic + anionic) surfactant mixtures composed of dodecyltrimethylammonium bromide (DTAB) and dioctyl sulfosuccinate sodium salt (AOT) mixed at various mole ratios are prepared and their spreading behavior on both mucin and cystic fibrosis (CF) mucus models is investigated for the first time in the literature. Synergistic interaction is obtained between the components of the DTAB/AOT mixtures, and this interaction has enhanced the spreading of the formulation drop on both the mucin and CF mucus models when compared with the spreading performances of selected conventional surfactants. It is proposed that the catanionic surfactant mixtures, especially when mixed at the molar ratios of 8/2 and 7/3 (DTAB/AOT), improve the spreading even on the cystic fibrosis sputum model. As it is vital to transport a sufficient amount of drug to the targeted region for the treatment of diseases, this study presents an important application of the fundamentals of colloidal science to pharmaceutical nanotechnology.

Keywords: Marangoni flow; catanionic surfactants; mucus; pulmonary drug delivery; spreading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions / chemistry
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid
  • Cations / chemistry
  • Cattle
  • Chloride Channel Agonists / administration & dosage*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / pathology
  • Dioctyl Sulfosuccinic Acid / chemistry
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Mucins / metabolism
  • Quaternary Ammonium Compounds / chemistry
  • Respiratory Mucosa / metabolism*
  • Sputum / drug effects
  • Sputum / metabolism
  • Surface Tension / drug effects
  • Surface-Active Agents / chemistry*
  • Viscosity


  • Anions
  • Cations
  • Chloride Channel Agonists
  • Mucins
  • Quaternary Ammonium Compounds
  • Surface-Active Agents
  • Dioctyl Sulfosuccinic Acid
  • decyltrimethylammonium