Cinnamic acids for respiratory diseases: biological evidence and drug-delivery strategies

Abstract Chronic respiratory diseases remain a major global public health burden and continue to pose significant challenges to current therapeutic strategies. In this context, cinnamic acids have attracted attention due to their reported anti-inflammatory, antioxidant, antimicrobial, and bronchodilator activities. However, whether these biological effects are sufficient to support their development as respiratory therapeutics remains unclear. This review was guided by the hypothesis that the therapeutic potential of cinnamic acid derivatives in respiratory diseases depends not only on their capacity to modulate inflammatory and oxidative pathways, but also on their pharmacological specificity, pulmonary exposure, formulation suitability, and translational feasibility. A structured literature review was conducted using PubMed and ScienceDirect, to identify studies addressing cinnamic acid derivatives, respiratory diseases, respiratory-relevant infections, and drug-delivery strategies. The studies indicate that compounds such as cinnamic acid, cinnamaldehyde, ferulic acid, and caffeic acid can modulate disease-relevant mechanisms, including cytokine production, oxidative stress, epithelial barrier dysfunction, macrophage activation, alveolar fluid clearance, fibrotic remodeling, and antimicrobial or antiviral responses in respiratory-relevant models. Nevertheless, the current evidence base remains predominantly preclinical and is limited by short-term experimental designs, scarce toxicological assessment, lack of well-designed clinical trials, and substantial variability in compounds, botanical sources, formulations, and disease models. Nanotechnology and other drug-delivery strategies have been proposed to improve stability, bioavailability, and pulmonary targeting of cinnamic acid derivatives, with proof-of-concept studies suggesting potential advantages for enhancing local delivery and reducing systemic exposure. However, most formulation studies remain exploratory and lack integrated assessment of long-term safety, scalability, pulmonary deposition, and regulatory feasibility. Overall, this review supports the biological plausibility of cinnamic acid derivatives as candidates for respiratory drug development, while emphasizing that their translational value will depend on resolving key biopharmaceutical and regulatory barriers.