Fabrication of 3D Printed Microneedle Patch for the Simultaneous Delivery and Detection of Melatonin from Interstitial Fluid.

Interstitial fluid (ISF) offers a potential alternative to invasive blood sample collection for biomolecule analysis. Microneedle (MN) patch application can collect ISF in a minimally invasive manner. Polyethylene glycol diacrylate MN patch was fabricated using optimized masked stereolithography-based 3D printing technique. Different 3D printing parameters including ink formula, exposure time, layer thickness, lift speed and distance, printing angle were optimized to fabricate pyramidal MN array. MN patch was characterized for design features, mechanical strength, in vitro, ex vivo and in vivo aspiration of fluid. MN patch aspirated 15 ± 2 µl ISF after application for 10 min in the rat model. Circadian rhythm controlling melatonin hormone was analyzed from ISF. The melatonin concentration ranged from 81 ± 13 to 178 ± 11 pg/ml and 94 ± 20 to 202 ± 6 pg/ml in ISF and serum from light to dark cycle, respectively. Furthermore, two different concentrations of melatonin were loaded in the MN patch during the 3D printing process. The two patches, blank MN patch for collection of ISF for melatonin detection (melatonin aspiration patch) and melatonin loaded patch for delivery (melatonin delivery patch) were simultaneously applied on the rat. Melatonin concentration increased by 4.6 and sixfold in ISF and serum, respectively after application of 20 µg melatonin MN patch, which was determined by blank MN patch application. Taken together, mSLA 3D printing technique can be used to fabricate melatonin loaded MN patch to deliver and collect ISF for melatonin analysis.