A BREAKTHROUGH in insulin delivery could one day eliminate the need for the invasive needles that many people with diabetes rely on. Scientists have successfully demonstrated a topical insulin treatment in mice, minipigs, and lab-grown human skin samples — an achievement long considered impossible. The challenge has always been the skin’s effective barrier. Insulin molecules are relatively large and hydrophilic, which prevents them from penetrating the skin’s oily outer layers, known as the stratum corneum. A team led by scientists at Zhejiang University has developed a solution. “The skin-permeable polymer may enable non-invasive transdermal delivery of insulin,” they write, “relieving patients with diabetes from subcutaneous injections and potentially facilitating the patient-friendly use of other protein- and peptide-based therapeutics.” The researchers engineered a delivery system that leverages the skin’s natural pH gradient, which is slightly acidic on the surface and becomes more neutral in deeper layers. Their solution is based on a biocompatible polymer called OP, which changes its properties with pH. On the skin’s surface, the OP polymer carries a positive charge, allowing it to bind to the skin’s lipids. As it moves to deeper layers with a more neutral pH, it loses that charge and releases, effectively carrying its cargo through the barrier. By binding insulin to this polymer to form a conjugate called OP-I, the researchers created a method for the hormone to hitch a ride into the body. In tests on diabetic mice, the OP-I conjugate reduced blood glucose to normal levels within an hour, with an efficacy matching that of traditional injections, and maintained stable levels for up to 12 hours. Subsequent experiments on diabetic minipigs, which are biologically closer to humans, showed comparable results, with glucose levels normalizing within two hours and remaining stable for 12 hours. Importantly, no signs of inflammation were observed, suggesting minimal side effects, although more extensive human trials are needed for confirmation. The implications extend beyond insulin. The researchers note that “OP conjugation is versatile for the transdermal delivery of biomacromolecules such as peptides, proteins, and nucleic acids, with broad therapeutic applications.” The details of this promising research were recently published in the journal Nature.(SD-Agencies) | 