Fabrication and characterization of enteric microneedle patches for oral delivery of small and macromolecule compounds

Needle patches are commonly used for administration of therapeutics via several routes such as transdermal and buccal delivery. Researchers have further used this strategy for oral delivery of poorly permeable therapeutics by direct injections in the gastrointestinal epithelium, which raises safety concerns about the long-term adverse effects. This study aims to investigate the use of microneedles for oral delivery of compounds with a wide range of molecular weights. For this purpose, we produced fully enteric microneedle patches for unidirectional release by casting. The microneedles presented a length of 175 µm (minimum mucus thickness in the small intestine) to minimize the risk of epithelial damage. A homogeneous drug distribution in the patches was verified by confocal Raman spectroscopy and fluorescence microscopy. Microneedle patches appeared to increase the force displacement in porcine small intestine compared to negative controls (4.4 ± 2.1 mN and 1.8 ± 0.9 mN, respectively), which suggest that microneedles could increase the retention time of oral devices in the gastrointestinal tract. Additionally, the length and integrity of the needles were not affected during the mechanical test studies. In vitro studies at gastric and intestinal pH confirmed successful enteric release and permeation of the drug compounds through biosimilar mucus independently of the molecular weight. The proximity of the patch to the membrane increased the permeation rate, which indicates the potential advantage of microneedles to increase the retention time of more complex devices such as self-unfolding foils, which can ensure drug release in close proximity to the epithelium.