Drug Absorption by the Respiratory Mucosa: Cell Culture Models and Particulate Drug Carriers

Abstract

The inhalation route is of increasing interest for both local and systemic drug delivery, including macromolecular biopharmaceuticals, such as peptides, proteins, and gene therapeutics. In addition to appropriate aerosolization for deposition in relevant areas of the respiratory tract, therapeutic molecules may require an advanced carrier system for safe and efficient delivery to their target. Two approaches to obtain novel carrier systems for pulmonary drug delivery are large porous microparticles with a low aerodynamic diameter and lectin-functionalized liposomes. Epithelial cells of alveolar or bronchial origin, obtained either from patient material or from established cell lines, can be grown on permeable filter supports, resulting in polarized monolayers with functional intercellular junctions. With such in vitro models, transport of drugs into pulmonary epithelial cells and/or across the air-blood barrier, as well as the effect and efficacy of novel drug carrier systems can be systematically studied.

Nanomedicine in pulmonary delivery

“…[201][202][203][204][205] The cell lines used include A427, A549, HBE14o, and the Calu line (-1, -2, and -3). [205][206][207][208][209][210] These are immortal (continuous) cell lines and hence have different membrane structural features compared with mortal cell lines which influence drug absorption and efflux. For example, A549 cell line represents the alveolar type II pulmonary epithelial cell, and has been reported to be an ideal model to study the metabolic and macromolecule mechanisms of drug delivery at the alveolar pulmonary epithelium because the endocytic ability of the pulmonary epithelium and localization of cytochrome P450 systems is largely a function of type II pneumocytes.…”

Inhaled chemotherapy in lung cancer: future concept of nanomedicine

“…This property makes them an ideal carrier system for proteins and peptides. 155,156 In order to encapsulate a drug, a number of factors, including heat, pH, oxygen, solvents, moisture, and mechanical stresses, must be assessed. Preparation for aerosol delivery can be undertaken using spray-drying, emulsion-solvent evaporation, phase separation, emulsion-solvent diffusion, and supercritical fluid technology.…”

Polymeric Nanocarriers for Transport Modulation across the Pulmonary Epithelium: Dendrimers, Polymeric Nanoparticles, and their Nanoblends

“…Calu-3 cells (passages [35][36][37][38][39][40][41][42][43][44][45] were seeded at a density of 1×10 6 cells per well in 24-well plates, and allowed to grow to confluence. The monolayer confluence was confirmed by staining select wells for ZO-1 and subjecting them to fluorescence spectrometry as detailed earlier, a day before commencing the uptake studies.…”

“…Calu-3 is a well differentiated and characterized cell line derived from human bronchial sub mucosal glands [23]. Besides producing tight junctions, Calu-3 is one of the few respiratory cell lines capable of expressing many important characteristics of the bronchial epithelium in vitro, such as the production of airway surface liquid, mucin excretion, cilia, and other immunologically active substances that make Calu-3 an appropriate candidate for elucidating tracheobronchial permeability in vitro [23,45]. Calu-3 cells were grown under a liquid-covered culture for 48 h, after which the medium in the apical compartment was removed and the cells were allowed to grow under AIC.…”