Closed-Loop Patch Provides Prolonged Heparin Delivery

A new study describes a transcutaneous patch that can sense activated thrombin and release heparin on demand to prevent coagulation and thrombii.

Developed by researchers at North Carolina State University (NC State, Raleigh, USA) and the University of North Carolina (UNC, Chapel Hill, USA), the new patch incorporates multiple polymer microneedles that unite hyaluronic acid (HA) and heparin. The polymer is modified to be responsive to thrombin, an enzyme that initiates clotting in the blood. When elevated levels of thrombin enzymes in the bloodstream contact the microneedle, they break the specific amino acid chains that bind the heparin to HA, releasing it into the blood stream.


The researchers tested the HA-Heparin smart patch in a mouse model. In the first experiment, mice were left untreated, given a shot of heparin, or given the HA-heparin smart patch; they were injected with a fatal dose of thrombin 10 minutes later. Fifteen minutes after the thrombin injection, only the mice that received no treatment died. In a second experiment, thrombin was injected six hours after surgical treatment. Fifteen minutes later, all of the mice with the HA-Heparin smart patch were fine, but 80% of the mice that received the thrombin shot had died. The study was published on November 25, 2016, in Advanced Materials.

“Our goal was to generate a patch that can monitor a patient's blood and release additional drugs when necessary; effectively, a self-regulating system,” said co-corresponding author Zhen Gu, PhD, an associate professor in the joint biomedical engineering program at NC State and UNC. “We're excited about the possibility of using a closed-loop, self-regulating smart patch to help treat a condition that affects thousands of people every year, while hopefully also driving down treatment costs. We're now looking for funding to perform additional preclinical testing.”

“We will further enhance the loading amount of drug in the patch. The amount of heparin in a patch can be tailored to a patient's specific needs and replaced daily, or less often, as needed,” said co-lead author Jicheng Yu, MSc, a Ph.D. student in Dr. Gu's lab. “But the amount of Heparin being released into the patient at any given moment will be determined by the thrombin levels in the patient's blood.”

Heparin is a highly sulfated glycosaminoglycan, widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. Although it is used principally for anticoagulation, its true physiological role in the body remains unclear, as blood anti-coagulation is achieved mostly by heparin-sulfate proteoglycans. It has been proposed that the main purpose of heparin is defense against invading bacteria and other foreign materials, and not anticoagulation.

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