Dually ionic hydrogels with pH and temperature sensitive properties used for therapeutic protein delivery

Injectable hydrogels with dual ionic properties, biodegradability and low cytotoxicity have been developed by South Korean scientists to deliver proteins therapeutically.

Doo Sung Lee and colleagues from Sungkyunkwan University developed an amphoteric copolymer to form dually cationic and anionic hydrogels, in response to pH and temperature changes. The amphoteric nature of the polymer means it should bind to both cationic and anionic biomolecules, and helps sustained co-delivery of them.

The copolymer can reversibly change between sol and gel, depending on the pH and temperature conditions induced

The copolymer is a free flowing sol at mildly acidic and alkaline pH, which means the hydrogel can be injected into the body using those conditions. Lee’s team was then able to study its ability to deliver proteins therapeutically, choosing the anionic human growth hormone (hGH) as the model protein. Preliminary results show promise, they say, as the hGH-loaded hydrogels lasted more than three days in vivo with minimal initial bursting. The hydrogel was also confirmed as being biodegradable with low cytotoxicity in accordance with ISO (International Organization for Standardization) guidelines. Lee adds: ‘We would like to prove [the hydrogel’s] capability to delay the release of cationic bioactive molecules, such as bone morphogenetic protein and transforming growth factor beta for tissue regeneration.’

Vitaliy Khutoryanskiy, a pharmaceutical scientist at the University of Reading, UK, believes that the materials could be of potential interest to other areas of drug delivery. ‘A free flowing polymer solution containing a therapeutic agent that can turn into a gel upon administration into the eye could be used for improving bioavailability for ophthalmic drugs,’ he says. ‘However, in this case these materials should ideally form transparent gels and should not cause ocular irritation.’

For now, the hydrogels face other challenges if they are to be seriously considered for future uses in medicinal applications. For example, Lee suggests that the release of biomolecules at desired sites needs to be controlled, the stability of encapsulated molecules needs to be improved for long term use and the biocompatibility of the synthesised materials needs to be enhanced.