Skin-Covered Hydrogels—A Novel Zero-Order Drug Delivery System

In most drug delivery devices today, drugs are released out of the device in an immediate or first-order manner, implying that the rate of release is high at the outset and decreases exponentially thereafter. As a result, undesirable side effects are often observed, and moreover, increased dosing frequencies are needed to achieve the necessary therapeutic effect. Zero-order drug delivery devices have the potential to overcome these issues by releasing drugs at a constant rate; thereby maintaining drug concentrations within the therapeutic window for an extended period. Till date, researchers have explored several ways to accomplish zero-order release; however, the majority of these are complex, time-consuming, and difficult to manufacture.<br/><br/>Here, we design a simple way to achieve zero-order release of various water-soluble solutes out of any given hydrogel. Our solution is to create a thin polymeric skin around the hydrogel using an inside-out strategy. We show that uniform polymeric skins with a tunable thickness of 10−100 μm can be easily achieved using our technique. For zero-order release to occur, the skin is made mostly from a hydrophobic monomer, but with small amounts of a hydrophilic monomer. This generates hydrophilic domains in the skin, and we will demonstrate that this combination leads to a zero-order response. Additionally, we show that it is possible to tune the release rate by varying the thickness of the skin and the concentration of the hydrophilic monomer.