Neotype Intelligent Drug Delivery Device: Biorhythm-Mimicking Growth Hormone Patch

• • Three-stage rhGH release at 1, 4, and 6 h post-administration replicates the endogenous overnight GH pulses, achieving stabilized IGF-1 secretion; this temporal precision is critical because conventional daily subcutaneous injections fail to synchronize rhGH levels with natural rhythms, leading to suppressed endogenous GH production and suboptimal therapeutic indexes. • • The burst-release module incorporates anhydrous citric acid and sodium bicarbonate as an effervescent agent, while delayed-release modules use a water-insoluble poriferous shell and swellable core with 10 mg mL−1 (Module 2) and 1 mg mL−1 (Module 3) hydroxypropyl methylcellulose (HPMC); these formulation parameters directly govern the release kinetics and are essential for scalable manufacturing. • • In GH gene knockout mice and healthy rats, the BRIGHT patch increased body length, bone length, and bone quality without increases in weight or body fat, demonstrating a therapeutic index superior to subcutaneous rhGH injection and effervescent-agent-doped microneedles; this addresses the clinical need for growth-promoting effects without metabolic side effects. • • Transcriptome analysis revealed that the BRIGHT patch affects more differentially expressed growth-associated genes than subcutaneous rhGH solution or effervescent-agent-doped microneedles, providing mechanistic evidence that biorhythm-mimicking delivery enhances growth-related biological processes at the transcriptional level.