APPLICATION OF ORGANOTYPIC IN VITRO HUMAN CELL CULTURE MODELS FOR RESEARCH AND DEVELOPMENT OF INHALATION PHARMACEUTICAL FORMULATIONS TARGETING THE PROXIMAL AIRWAYS.

Delivery of pharmaceuticals via inhalation is a potentially useful alternative to intravenous injection for drugs that are unstable or poorly absorbed after oral administration; for chronic disease conditions that require frequent administration: or therapeutics for which the airways are the intended target. The proximal airways are common targets for drugs Intended to treat inflammatory conditions associated with rhinitis, asthma and chronic bronchitis. In addition, intranasal delivery of vaccines and systemically-targeted drugs has been the focus of significant recent interest. However, inhalation drug delivery via the proximal airways faces challenges in achieving effective doses due to rapidity of mucociliary clearance as well as potential irritation/toxicity issues. These issues are best addressed early in formulation development prior to costly animal studies or clinical trials. This article briefly reviews the application of organotypic in vitro tissue culture models for assessing drug disposition, toxicity and efficacy of inhalable formulations intended for administration via the proximal airways and discusses the use of these models for efficacy screening of pharmaceuticals that target various respiratory diseases.

AFT-100, AIR-100, Ashthma, Chronic pulmonary disease (COPD), Disease model, Drug delivery, GMP, Goblet cell hyperplasis, Inflammation, ,Inhaled pharmaceuticals, Mucus production, Proximal airway, Rhinitis, TEER, TH2 cytokines

FITC-dextran, IL-13, IL-4