The formulation stage offers many opportunities for scientists to impart controlled release to multidrug dosage forms. Hydrogels, extremely hydrated polymer gels that hold many times their weight in trapped water, are a drug-delivery mechanism that can be manipulated to change the release profiles of APIs (1).Rather than using commercially available materials, which is the traditional method, a team of researchers at the Massachusetts Institute of Technology (MIT) created designer peptides from scratch that had both hydrophobic and hydrophilic parts. When exposed to water, the peptides' hydrophobic parts assemble into a hydrogel scaffold, explains Shuguang Zhang, associate director of MIT's Center for Biomedical Engineering. The scaffold, a nanofiber that contains nanopores, can house small- and large-molecule drugs and carry more than one API at a time.
By modifying the hydrogel scaffold's peptides, scientists could provide different release profiles for separate APIs. The scaffold could include peptides with physical hooks that are specific to particular receptors in the body. An API associated with a hook would be released earlier than an API housed in the scaffold's micropores, says Zhang.
The nanopores in the scaffold are components or "harbors" that protect biological drugs from water ingress, Zhang says. Because the scaffold is stable at high temperatures, it also protects proteins from becoming denatured. The team's recent research shows that protein drugs are still functional when they emerge from the hydrogel scaffold, which could be used to deliver erythropoietin by injection, says Zhang (2).
Scientists could modify the hydrogel scaffold to alter the release profile of the drugs it carries. Zhang's team engineered specific enzymes to cut a particular site on the peptide chain to degrade the scaffold quickly, which increased the release rate. If the scaffold remained intact longer, it would release drugs slowly. Scientists can engineer the scaffold to resist enzymatic degradation, but this technique is difficult, says Zhang. Another way to modify the release profile would be to change the thickness of the nanopore enclosures that house an API.
The hydrogel scaffold is safer for patients than other natural and synthetic materials. In contrast with animal-derived materials, MIT's hydrogel scaffold is entirely aseptic and has not provoked any immune response, Zhang says. The scaffold is easier for the body to process and reuse than synthetic polymeric materials, he adds. Innocuous polymers sometimes degrade into toxic monomers. In contrast, enzymes in the body break down the hydrogel scaffold's peptides into harmless amino acids. The team's isotope-labeling study found that the hydrogel scaffold breaks down at a rate of 10% every two weeks, an "almost perfect" rate for many drug-delivery applications, says Zhang. A conventional isotope takes two weeks to degrade by 10%.