Innovative Formulations for Controlled Drug Delivery to the Lungs and the Technical and Toxicological Challenges to Overcome

Inhalation of therapeutic aerosols has a long tradition and is, moreover, regarded as a safe and efficient route of drug administration to the respiratory tract. Especially, the targeting opportunities of this approach are beneficial for the treatment of numerous airway diseases. However, the rapid decay of local drug concentration and the resulting short-term duration of action of conventional medications necessitates several daily inhalations, which is clearly in conflict with a patients' convenience and compliance. Recent progress in pharmaceutical engineering has provided promising drug delivery vehicles (e.g., liposomes, nanoparticles and thermo-responsive preparations) allowing for a sustained release of the encapsulated medication at the target site. Nevertheless, aspects such as generating tailored aerosols from these formulations (including stability during aerosolization) and the choice of biocompatible excipients remain considerable challenges, which need to be addressed in order to optimize inhalation therapy. Therefore, toxicology issues raised by these novel drug delivery vehicles with respect to physicochemical and material properties and biocompatibility are described in this review. This brief overview is intended to serve as a foundation to prompt future advancement in the field of controlled drug delivery to the lungs.