Microneedle-based insulin transdermal delivery system: current status and translation challenges

Autonomous Untethered Microinjectors for Gastrointestinal Delivery of Insulin

“…The injection route of insulin delivery poses several limitations, including poor patient compliance and increased risk of infections, thus compromising optimal outcomes. Transdermal and oral insulin delivery routes are superior in terms of compliance and have been investigated extensively over the past several decades. , Transdermal insulin delivery systems such as microneedle patches have been explored as alternatives as they are significantly less painful than hypodermic or subcutaneous needles. , On applying pressure, the microneedles create minuscule disruptions in the stratum corneum, which is the main physical barrier for transporting large molecules like insulin across the skin. − However, transdermal delivery using microneedle patches has proven challenging due to the difficulty of achieving therapeutic levels of insulin. An alternative to transdermal delivery, the oral administration of insulin has been a long-sought-after goal because of the wide acceptance of the oral route of drug delivery. − The oral route for insulin delivery has been elusive to date due to several significant hurdles: (i) the degradation of insulin by enzymes like proteases and the acidic pH in the stomach, (ii) the passage of insulin through the mucus barrier that lines the GI epithelium, and (iii) the movement of insulin across the intestinal epithelial cells held together by tight-junction proteins. − Over the past few decades, the use of permeation enhancers (PE) such as ethylenediaminetetraacetic acid (EDTA), glyceryl monocaprate, and sodium cholate have increased both the paracellular and transcellular transport of insulin in the GI tract. − However, most PEs are developed based on epithelial monolayer cultures and isolated tissue, which often results in low bioavailability in live animals and therefore has limited potential for clinical translation. , …”

Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) as an insulin carrier in silk fibroin hydrogels for transdermal delivery via iontophoresis

“…Diabetes mellitus is a metabolic disease as identied with hyperglycaemia, glycosuria, and hyperlipidemia; they are caused by either low insulin secretion by cells or low insulin binding efficiency, resulting in high blood glucose levels. [1][2][3] Diabetes mellitus can be classied into type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes, and special types of diabetes. 4 T1DM is known as the autoimmune diabetes as characterized by the absolute insulin deciency due to the damaged pancreatic beta-cell function.…”

In Situ-Forming Protein-Polymer Hydrogel for Glucose-Responsive Insulin Release

“…They are often considered for smart drug delivery applications. − For instance, dynamic covalent phenylboronic acid (PBA)–diol ester bond-based HGs have demonstrated glucose-responsive behavior and promise to be smart insulin delivery systems for maintaining blood glucose levels in insulin-dependent diabetes patients. − PBA–diol ester bonds are susceptible to break in the presence of d -glucose, the most abundant carbohydrate in the human body. The advantages of using PBA-based glucose-responsive HGs are their chemical stability and minimum toxicity, which enables long-term use in preclinical studies. , In current practice, PBA-containing synthetic polymers are derived from radical polymerization reactions. − Therefore, these materials are exclusively used for external use as catheters and microneedle patches due to their nonbiodegradability. ,− Recently, diol-containing synthetic polymers, such as polyvinyl alcohol (PVA), are crosslinked with bis-PBA-based molecules to produce injectable glucose-responsive insulin-releasing HGs. − Noticeably, for most glucose-responsive HGs, the correlation between bulk rheological properties and glucose-responsive insulin release profile remains elusive. Further, the use of biomacromolecules in the HG composition is desired to improve biocompatibility, biodegradability, and, most importantly, sustainability for future biomedical applications .…”