Formulation Development Forum: Hydrogels for Long-Sustained Release

Researchers from the University of Cambridge in England have developed injectable, reformable, and spreadable hydrogels that can be loaded with proteins or other therapeutics. The hydrogels contain up to 99.7% water by weight, with the remainder primarily made up of cellulose polymers held together with cucurbiturils or barrel-shaped molecules that act as miniature “handcuffs,” according to an Aug. 15, 2012, University of Cambridge press release.

“The hydrogels protect the proteins so that they remain bioactive for long periods, and allow the proteins to remain in their native state,” said Oren Scherman, professor in the Department of Chemistry at the University of Cambridge, in the university release and who also led the research. “Importantly, all the components can be incorporated at room temperature, which is key when dealing with proteins that denature when exposed to high heat.”

The researchers prepared the self-assembled hydrogels with high water content (up to 99.5%) and tuned mechanical properties. The protein-release characteristics were investigated to determine the effect of both the protein molecular weight and polymer loadings of the hydrogels on the protein-release rate. Sustained release of bovine serum albumin was observed over the course of 160 days from supramolecular hydrogels containing only 1.5% (by weight) polymeric constituents (1).

The hydrogels were capable of delivering sustained release of the proteins they contain for up to six months compared with the current maximum of three months, according to the university release. The rate of release can be controlled according to the ratio of materials in the hydrogel. In addition to broadening the time for content release, the hydrogels use less non-water material than current technology. “The extra material serves as a type of scaffolding holding the hydrogel together, but it can affect performance of the cargo contained within it, so the less structure-forming material contained within the hydrogel, the more effectively it will perform,” according to the university release.

Potential applications for the hydrogels are protein-based drugs for chronic diseases, such as hormone therapy, wound healing, and insulin treatment. The team is currently working with researchers from the Brain Repair Center in the Department of Clinical Medicine on how the technology might be used as a possible treatment for brain cancer.

Additionally, the long-term sustained release would be beneficial for administering drugs in geographic areas where access to medicines and daily drug administration may be difficult or as a means to increase patient compliance. “There’s been a lot of research that shows patients who need to take a pill each day for the rest of their lives, especially HIV patients in Africa who do not show any obvious symptoms, will take the pills for a maximum of six months before they stop, negating the point of taking the medication in the first place,” said Eric Appel, doctoral student and co-author of the recent research article, in the university release (1). “If patients only have to take one shot that will give them six month’s worth of medication, we’ll have a much greater chance of affecting an entire population and slowing or stopping the progression of a disease.”

Reference

1. O.A. Scherman, Biomaterials33 (18), 4646–4652 (2012).