Drug delivery based on circadian rhythm: mechanisms, applications, and prospects

Biological circadian rhythm is a ubiquitous phenomenon in living organisms that regulates numerous physiological and biochemical processes. In the field of drug delivery, it exerts profound impacts on the pharmacokinetics and pharmacodynamics of drugs, as well as the efficiency and therapeutic outcomes of drug delivery. Accordingly, optimizing drug delivery strategies based on human circadian rhythms to achieve optimal therapeutic efficacy has emerged as a highly popular research direction. Compared with conventional drug delivery systems (DDS), circadian rhythm-adapted DDS can precisely control the release time and dosage of drugs to align with the intrinsic rhythms of hormone secretion, gene expression and disease progression in the body, thereby enhancing therapeutic efficacy, reducing toxic and side effects, and improving patients' medication compliance under certain circumstances. Such DDS are mainly classified into two categories: circadian rhythm-compliant and circadian rhythm-modulating drug delivery systems. The former adopts controlled or sustained drug release to match drug administration with the optimal time window for drug absorption in organisms so as to boost therapeutic effects, while the latter employs chemical ligands targeting the circadian rhythm system to interfere with circadian rhythm expression, facilitating drug delivery and pharmacological action. To date, circadian rhythm-based DDS have been extensively investigated and applied in the treatment of metabolic diseases, cardiovascular diseases, cancers and many other disorders. This review elaborates on the significant influences of biological circadian rhythms on drug delivery and their implications for the optimization of drug delivery systems, summarizes drugs capable of modulating circadian rhythms, and discusses the key challenges that need to be addressed to further broaden the application of circadian rhythms in the field of drug delivery.