Biodegradable microneedles for transdermal sitagliptin delivery: in vivo insights into enhanced diabetes management

Microneedles (MNs) offer a promising alternative for transdermal delivery of hydrophilic drugs such as sitagliptin, evading the gastrointestinal side effects associated with oral administration. Thus, the study focuses on the transdermal delivery of sitagliptin, an antidiabetic drug that inhibits dipeptidyl peptidase-4 (DPP-4). The research includes the formulation and in-vitro, ex-vivo, and in-vivo characterization of MNs for sitagliptin delivery. MN molds were fabricated using Stereolithography (3D Printing), and biocompatible MNs were made from hyaluronic acid (HA), chitosan, polyvinylpyrrolidone and polyvinyl alcohol (PVA). Sitagliptin MNs with PVA (SMP) and HA (SMH) exhibited favorable physical and mechanical properties, with drug content of 3.5 ± 0.14 mg/g and 3.8 ± 0.12 mg/g, respectively. SMH showed superior skin penetration due to sharper, stiffer tips. Ex-vivo studies using rat skin indicated that the SMH yielded a higher cumulative permeation (36.58%) compared to SMP (24.04%). Additionally, sitagliptin primarily accumulated in the epidermis, with approximately 56% for SMH and 50% for SMP. In-vivo results demonstrated that both SMP and SMH effectively lowered fasting blood glucose levels, with SMH notably improving postprandial glucose and insulin levels. Overall, HA-based biodegradable microneedles present a promising, minimally invasive strategy for sitagliptin delivery, enabling effective type 2 diabetes management while avoiding its gastrointestinal side effects. 3D printing successfully fabricated microneedle molds for drug delivery. Biocompatible microneedles (MN) deliver sitagliptin for type 2 diabetes management. MN showed enhanced skin permeation and drug deposition in ex-vivo studies. Hyaluronic acid MN improved postprandial glucose and insulin regulation in-vivo. Minimally invasive MN offer a promising alternative for diabetes management.