Biorhythm-mimicking growth hormone patch

Timing dosing throughout the day impacts the therapeutic efficacy and side effects of medications. Thus, optimizing release profiles to synchronize drug concentrations with natural rhythms is critical for optimal therapeutic benefits. However, existing delivery systems are still inefficient in delivering drugs in a biorhythm-mimicking fashion. Here we describe a biorhythm-inspired growth hormone transdermal microneedle patch with multistage drug release that mimics the natural rhythm of human growth hormone secretion at night. Programmed drug release is achieved by combining a ‘burst-release’ module with several ‘delayed-release’ modules. Compared with the subcutaneous daily injections currently used in clinics, the patch exhibits enhanced efficacy in terms of longitudinal bone growth and bone quality, leading to bone length increases of ~10 mm and ~5 mm in healthy rats and growth hormone gene knockout mice, respectively. Our findings reveal that the biorhythm-mimicking release pattern significantly enhances growth hormone bioavailability and effectively regulates the growth-related biological process, thus boosting the secretion of insulin-like growth factor-1 and ultimately promoting bone growth.