Abstract:
OBJECTIVE To design microneedle patches for daytime and nighttime administration of growth hormone to stimulate the circadian rhythm of endogenous growth hormone secretion under human physiological state, effectively alleviate the pain of subcutaneous injection and improve the compliance of patients.
METHODS Microneedle patches were prepared by the casting method. The surface morphology of microneedles was observed by the optical microscope and scanning electron microscope. The optimum process conditions for the preparation of microneedles were determined by
in vitro release experiments, including optimizing the UV irradiation duration and the content of the crosslinking agent. The mechanical strength test and
ex vivo penetration experiment were applied to verify whether the microneedles can effectively penetrate the skin and achieve transdermal drug delivery. The biostability of the protein drug was determined by the circular dichroism spectroscopy. Two types of microneedle patches for daytime and nighttime administration respectively were assessed by loading different doses of growth hormone.
RESULTS The microneedles were orderly arranged with the complete and sharp needles observed by the microscope, and there was insignificant morphology change after drug release. Through the optimization of process conditions, when the UV irradiation duration was 7 min and the content of the crosslinking agent was 1.5%, the microneedle patch could effectively penetrate the rat skin and realize the stable release of growth hormone within 12 h, and the conformational change in the released protein drug was insignificant. By loading different doses of growth hormone into the microneedle patches, daytime and nighttime dosing patches had been prepared.
CONCLUSION In this study, the daytime and nighttime microneedle patches loading different dosages of growth hormone were prepared, which can comply with the circadian rhythm of growth hormone secretion in human physiological state, optimize the relationship between the administration time and dose of growth hormone, and realize on demanding releasing of growth hormone. In the future, the drug loading of microneedle patches can be further optimized to meet the personalized needs of people and realize individualized treatment.