Innovative formulations for controlled drug delivery to the lungs and the technical and toxicological challenges to overcome^#

Abstract

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.

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

“…In light of emerging chronotherapeutic approaches, various chronoprogrammable drug delivery systems have been developed . These approaches include chronomodulating infusion pumps, controlled‐release microchip strategies, floating pulsatile systems, nanotechnology, press‐coating approaches, micro‐electrochemical systems, osmotic pressure, microchips, liposomes, thermosensitive hydrogels, micro‐ and nanocarriers, and microparticle‐based systems.…”

“…In light of emerging chronotherapeutic approaches, 366 various chronoprogrammable drug delivery systems have been developed. 329,339,[367][368][369][370][371][372][373][374][375][376][377][378][379][380][381] These approaches include chronomodulating infusion pumps, controlled-release microchip strategies, floating pulsatile systems, nanotechnology, press-coating approaches, micro-electrochemical systems, osmotic pressure, microchips, liposomes, thermosensitive hydrogels, micro-and nanocarriers, and microparticle-based systems. The development of programmable time pumps has enabled the safe and highly effective delivery of combination chronotherapy protocols.…”

Ion-dependent slow protein release from in vivo disintegrating micro-granules

“…Diverse strategies for sustained drug delivery are under exploration, mainly based on porous materials, hydrogels, matrices, or other types of macroscopic, microscale, or nanoscale containers that hold the drug for its progressive leakage (Gilmore et al., 2016 ; Li & Mooney, 2016 ; Ali & Ahmed, 2018 ; Ghalei et al., 2018 ; Koshy et al., 2018 ; Wu et al., 2018 ; Meng et al., 2019 ). Such methodologies involve a non-drug-containing material that increases the complexity of the system and the fabrication process, often imposing chemical constraints and toxicological concerns (Sharma et al., 2012 ; Palombo et al., 2014 ; Aragao-Santiago et al., 2016 ; Shen et al., 2017 ). Recently, self-contained, self-disintegrating protein material in form of microparticles have been developed (Chen et al., 2020 ; Sánchez et al., 2020 ), suited for a slow protein release in vivo (Sánchez et al., 2020 ; Serna et al., 2020 ; López-Laguna et al., 2021 ).…”