Transdermal Microneedles for Insulin Delivery

Diabetes is a chronic metabolic disease that occurs when there is a deficiency in the production of insulin by the pancreas or when the body cannot effectively use the insulin it produces. Therefore, the treatment of diabetes aims to control the levels of glucose in the blood, which involves many different approaches, including insulin therapy many times. To date, even though many strategies have been proposed as alternative administration routes for insulin, subcutaneous injections still the most common administration route. To overcome the disadvantages imposed by the daily subcutaneous injections of insulin and to increase patient compliance, this thesis aimed to develop stable coated microneedles for rapid transdermal delivery of insulin. For that, polymeric microneedles made of a biocompatible resin class I were developed using 3D printing technology and studied along with a commercial metallic microneedle. The penetration studies showed that the 3D printed MNs presented superior penetration capacity compared to the metallic microneedles. To apply specific doses of insulin on the microneedles, an Inkjet printing technology was used. The SEM revealed the formation of fine layers on the microneedles without loss of insulin during the coating process. Moreover, Micro-CT showed that the films stayed onto the MNs surfaces during the piercing. In order to address the challenges with insulin instability, different polymers and sugars were used as drug carriers to preserve insulin integrity during the coating process as well as to form uniform coating layers and facilitate rapid release rates. Circular dichroism and Raman spectroscopy demonstrated that most of the carriers maintained the secondary structure of insulin in its native form in the films. Moreover, X-ray diffraction analysis revealed that the insulin-carriers tended to originate amorphous films. The release studies using Franz cell diffusion showed that insulin is quickly released from the coated microneedles within 30 min. Furthermore, the animal studies showed that the coated 3D printed microneedles promoted a similar initial profile release to the SC injections, followed by a more sustained release pattern for all tested insulins (bovine, aspart and glargine)