Silk fibroin microneedles loaded with melatonin for circadian rhythm regulation

Abstract

As a new type of transdermal drug delivery preparation, microneedles can improve the bioavailability of drugs and enhance patient compliance. This article develops a melatonin transdermal sustained-release microneedles using silk fibroin as the substrate. The silk fibroin in microneedles forms a SILK I crystal structure, which does not dissolve in the skin but has certain swelling properties. Microneedles have superior mechanical properties, and can puncture the skin to form a sustained-release channel in the dry state. After drug release is completed, wet microneedles can be pulled out. The results of in vitro transdermal experiments show that the effective drug release time of microneedles is significantly correlated with drug loading. The sustained release time of melatonin silk fibroin microneedles with a drug loading of 1 mg/tablet reach 11 h, with a cumulative release rate of over 85 %. The results of in vivo animal experiments show that silk fibroin melatonin microneedles can maintain a stable blood drug concentration for up to 8 h. The results of in vivo pharmacodynamics show that melatonin microneedles have significant therapeutic effects on insomnia model rats, improving disrupted circadian rhythms and alleviating anxiety.

Keywords: Insomnia; Microneedle; Silk fibroin; Transdermal delivery.