(Nanowerk Spotlight) Millions of patients who rely on biological medications face a frustrating reality: frequent injections. Modern drugs for conditions from diabetes to arthritis can’t be taken as pills because they break down in the digestive system. Instead, patients must maintain rigid injection schedules, sometimes requiring multiple shots per week. Missing doses compromises treatment, while frequent injections cause discomfort and reduce treatment adherence.
Controlling when and how quickly medications release into the body could transform treatment outcomes. Some diseases respond better to steady medication levels. Others need precisely timed bursts of treatment or deliberate delays between doses. Traditional drug delivery methods struggle to achieve these precise patterns. Even advanced approaches like polymer capsules or dissolvable implants typically release their contents in unpredictable ways, making it difficult to maintain optimal drug levels in the body.
Scientists have explored water-based gels called hydrogels as a potential solution. These materials can be injected under the skin as liquids, where they form soft deposits that hold medication. The challenge has been controlling exactly how these gels release their cargo. Most existing systems either release drugs too quickly or break down unpredictably, making it impossible to achieve specific dosing patterns.
Researchers at the Georgia Institute of Technology have now developed a hydrogel system that solves this control problem through an innovative dual-release mechanism. Their work, published in Advanced Functional Materials (“Injectable Hydrogels for Programmable Nanoparticle Release”), demonstrates precise control over medication release patterns lasting up to two weeks, with the ability to program burst, linear, or delayed release profiles.
The team created their hydrogel by combining two carefully designed components. The first is dextran, a sugar-based molecule chosen for its stability and compatibility with biological materials. They modified this dextran with special molecular switches called oxanorbornadiene (OND) groups. The second component is polyethylene glycol (PEG), a widely used medical polymer, equipped with reactive sulfur-containing groups. When mixed, these components form a gel network within minutes – slow enough to inject easily but fast enough to trap over 95% of the medication inside.
Schematic representation of formation and degradation of dextran-oxanorbornadiene/PEG-SH hydrogels. (Image: Adapted from DOI:10.1002/adfm.202409796; CC BY)
The system’s innovation lies in its dual-mechanism release control. The molecular switches break down in two distinct ways: one proceeds at a precise, predictable rate regardless of conditions, while the other responds to the gel’s environment. By combining different versions of these switches, the researchers can program exactly when and how quickly the gel releases its cargo. This two-part approach provides much finer control than systems relying on a single release method.
The researchers demonstrated this control using test particles the same size as many biological drugs – about 30 nanometers across. They achieved three specific release patterns: an initial burst release for immediate delivery, linear release providing steady medication levels, and delayed release with a programmed waiting period before activation. Most importantly, they showed these patterns could be maintained reliably over a two-week period, much longer than many existing systems.
The system meets practical requirements for medical use. Standard syringes can inject the gel components through routine needles. The formed gel has the right consistency to stay in place under the skin without causing irritation. Laboratory tests showed no toxic effects when the gel breaks down, and its components are based on materials already used in approved medical devices.
The technology proved particularly effective at protecting delicate biological cargo. The researchers used fluorescently tagged virus-like particles – complex protein structures that serve as a rigorous test of gentleness – to track the release process. These particles showed no structural damage or loss of function after release, maintaining more than 95% of their initial properties. This stability is crucial for biological drugs, which can easily lose effectiveness if their delicate molecular structure is disrupted during delivery.
The precision of release patterns could enable new treatment approaches. For vaccines, delayed release might better stimulate immune responses by mimicking multiple injections. For chronic conditions, steady release could maintain consistent drug levels while reducing injection frequency from weekly to monthly. The system’s modular nature means doctors could select specific release patterns to match individual patient needs.
Several specific challenges need addressing before clinical use. The release patterns, while reliable in laboratory conditions, must maintain their precision in the more complex environment of living tissue. The manufacturing process requires scaling up while ensuring consistent quality across batches – particularly challenging for a dual-component system. The researchers must also verify that the breakdown products from the gel remain safe when administered repeatedly over long periods. However, the system’s use of materials already approved for medical use and its straightforward design principles could help accelerate progress toward clinical trials.
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