Minimally Invasive Insulin Delivery in Subjects with Type 1 Diabetes Using Hollow Microneedles

Abstract

Background Microneedles have previously been used to deliver insulin to animal models, but not in human subjects. This study tested the hypothesis that hollow microneedles can deliver insulin to modulate blood glucose levels in subjects with type 1 diabetes in a minimally invasive manner. Methods This study was carried out in two adults with type 1 diabetes and evaluated bolus delivery of lispro insulin using a hollow microneedle compared to a catheter infusion set (9 mm). The study first determined the minimum insulin delivery depth by administering insulin from microneedles inserted 1, 3.5, and 5 mm into the skin of fasting subjects and then assessed the efficacy of insulin delivery from microneedles inserted 1 mm into the skin to reduce postprandial glucose levels. Blood samples were periodically assayed for plasma free insulin and plasma glucose levels for up to 3.5 h. Results The first phase of the study indicated that microneedles inserted at the shallowest depth of 1 mm within the skin led to rapid insulin absorption and reduction in glucose levels. Bolus insulin delivery followed by consumption of a standardized meal in the second phase revealed that microneedles were effective in reducing postprandial glucose levels. Subjects reported no pain from microneedle treatments, and there were no adverse events. Conclusions This study provides the first proof of concept that hollow microneedles can effectively deliver bolus insulin to type 1 diabetes subjects in a minimally invasive manner.

Microneedles for drug delivery: trends and progress

“…They also differ in shape, ranging from square, circular, flat tipped, sharp tipped, etc. (Henry et al, 1998;Park et al, 2005;Gupta et al, 2009;Swain et al, 2011;Kommareddy et al, 2013;Mansoor et al, 2013;Torrisi et al, 2013;Pierre & Rossetti, 2014). There has been a lot of research conducted on MNs for the delivery and monitoring of various drugs such as glucose control for diabetics (Ito et al, 2006;Nordquist et al, 2007;Ainslie & Desai, 2008;El-Laboudi et al, 2013;Taylor & Sahota, 2013;Ita, 2014), Alzheimer's disease (Wei-Ze et al, 2010), anticancer (Fang et al, 2008) and other conditions (Ezan, 2013).…”

“…They found that the use of biodegradable MNs increased skin permeability by three fold, which increase the delivery of drugs transdermally. Gupta et al (2009) used hollow MNs for bolus delivery of lispro insulin in comparison to catheter infusion. They found that MNs inserted 1 mm into human skin showed rapid insulin absorption with no pain observed from the volunteers in comparison to catheter infusion (Gupta et al, 2009).…”

Enhancement of skin permeation of vitamin C using vibrating microneedles

“…[8][9][10][11] Hollow microneedles have been coupled with a syringe for active drug infusion. [12][13][14] L-Ascorbic acid (vitamin C), a representative water-soluble vitamin, has a variety of biological, pharmaceutical and dermatological functions; it promotes collagen biosynthesis, provides photoprotection, causes melanin reduction, scavenges free radicals, and enhances the immunity (antiviral effect). [15][16][17][18][19] These properties are closely related to the well-known antioxidant properties of this compound.…”

Dermic diffusion and stratum corneum: A state of the art review of mathematical models

“…The microneedle piercing increases the skin permeability of the variety of compounds ranging from low molecular weight tracers to proteins, DNA and even nanoparticles [4,5]. However, the trauma suffered by the patients is still an issue, and a nanoneedle could prevent such problems, since there are studies relating positively the narrowness of the needle size and the minimization of trauma [6]. The common option of microneedles in many transdermal applications, despite the abovementioned issues, lies in the difficulty to diffuse the compounds through the skin, especially through the stratum corneum [7,8].…”