Self-Dissolving Microneedle Arrays for Transdermal Absorption Enhancement of Human Parathyroid Hormone (1-34)

Abstract

Human parathyroid hormone (1-34) (PTH) has been widely used as the subcutaneous injection formulation for the treatment of osteoporosis. In the present study, we developed an efficient transdermal delivery system of PTH by using dissolving microneedle arrays (MNs) composed of hyaluronic acid (HA) for the treatment of osteoporosis. PTH-loaded MNs, with needle length 800 µm, were fabricated via a micro-molding method. The stability of PTH in MNs was found to be 6-fold higher than that of PTH solution when stored at room temperature (15–20 °C) for one month. Micron-scale pores were clearly visible in rat skin following application of PTH-loaded MNs. PTH-loaded MNs were completely dissolved by 60 min following application to rat skin. The bioavailability (BA) of PTH relative to subcutaneous injection was 100 ± 4% following application of PTH-loaded MNs in rats. In addition, PTH-loaded MNs were found to effectively suppress decreases in bone density in a rat model of osteoporosis. Furthermore, no skin irritation was observed at the site of application in rats. These findings indicate that our dissolving MNs have a potential use in formulations for the transdermal delivery of PTH and for the treatment of osteoporosis.

Current trends in polymer microneedle for transdermal drug delivery

“…These findings indicate that the low absorption issue associated with oral dosage form or painful frequent injections could be replaced with self-administration of dissolving MNs. ( Naito et al, 2018 ) Monoclonal immunoglobulin G (IgG) Hyaluronic acid (HA) Dissolving MNs Moulding MNs (4 × 4) array and the length was 300 μm. The polymer MNs of (IgG) using HA provide rapid non-invasive intradermal protein delivery as well as maintain the stability of protein.…”

Acid-Treated Water-Soluble Chitosan Suitable for Microneedle-Assisted Intracutaneous Drug Delivery

“…The MNs prepared from these water-soluble polymers were effective for fast release of the encapsulated drug following insertion into skin [35]. Recently, for better biocompatibility, water-soluble natural polymers have gained special attention as MN materials [36]. In particular, clinically relevant (human injectable) polymers such as hyaluronic acid [37] are advantageous for relatively easy translation to clinical application when used in MN fabrication as a drug delivery vehicle.…”

Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

“…MNs-mediated transdermal protein and peptide delivery can also be used in other disease therapy, such as hypoglycemia 199 , osteoporosis 200 , cosmeceuticals 45 , and wound healing 201 .…”