ADDITIVE MANUFACTURING OF HOLLOW MICRONEEDLES FOR INSULIN DELIVERY

Microneedles (MN) are miniature devices capable of perforating painlessly stratum corneum and delivering active ingredients in the inner epidermal layers. Hollow microneedles (HMNs) are highly detailed objects due to their internal microchannels and thus, their fabrication with Additive Manufacturing (AM) is a challenging task. Vat polymerization techniques provide a sufficient accuracy for such microstructures. Differentiated from other approaches where stereolithography and 2-photon polymerization were adopted, this paper presents the 3D-printing of HMNs purposed for insulin delivery, using the more economic Liquid Crystal Display (LCD) method. First, different geometries (hexagon, square pyramid, beveled) were 3D printed with constant height and varying curing time, printing angle and layer resolution. Quality features in each case were captured with optical and scanning electron microscopy (SEM). The most promising geometry was found to be the beveled one due to the more refined tip area and the feasibility of non-clogged microchannel formation. Among printing parameters, printing angle proved to be the most influential, as it affects resin flow phenomenon during printing process. Lastly, optimized HMN geometry was the beveled configuration, where the average height was measured 900μm, 3D printing angle was set at -45°, the curing time was 10s per layer and the optimal layer height was 30μm.

Multivesicular Liposomes for Glucose-Responsive Insulin Delivery

An intelligent insulin delivery system is highly desirable for diabetes management. Herein, we developed a novel glucose-responsive multivesicular liposome (MVL) for self-regulated insulin delivery using the double emulsion method. Glucose-responsive MVLs could effectively regulate insulin release in response to fluctuating glucose concentrations in vitro. Notably, in situ released glucose oxidase catalyzed glucose enrichment on the MVL surface, based on the combination of (3-fluoro-4-((octyloxy)carbonyl)phenyl)boronic acid and glucose. The outer MVL membrane was destroyed when triggered by the local acidic and H2O2-enriched microenvironment induced by glucose oxidase catalysis in situ, followed by the further release of entrapped insulin. Moreover, the Alizarin red probe and molecular docking were used to clarify the glucose-responsive mechanism of MVLs. Utilizing chemically induced type 1 diabetic rats, we demonstrated that the glucose-responsive MVLs could effectively regulate blood glucose levels within a normal range. Our findings suggest that glucose-responsive MVLs with good biocompatibility may have promising applications in diabetes treatment.

Recent Advances in Insulin Delivery Devices and Modes of Insulin Therapy

The discovery of insulin was 100 years old till 2021. Insulin, the first diabetic medication, is now the safest and most effective glucose-lowering medication available. Despite its efficacy, the most significant challenge with insulin has been the prevalence of hypoglycemia, which has resulted in the majority of patients being prescribed optimum dosages. Insulin delivery devices include syringes, pens, and pumps. Soon, artificial pancreas (AP) by using a very closed-loop delivery method will be a big step towards the advancement of insulin delivery devices. This article looks at the invention of syringes, disposable, long-lasting pens, and smart connected pens, continuous intraperitoneal insulin infusion (CIPII) and patch insulin pumps, artificial pancreas and other medical devices. Hence, insulin administration that is both minimally invasive and non-invasive towards the advancement is required. We review the available information on the evolution of insulin delivery systems, focusing on the advantages and disadvantages of technology as well as anticipated advances. Due to the wide variety of technological solutions accessible via the international platform, only the most common methods essential to the patient’s care are detailed here in the article.