Influence of alginate backbone on efficacy of thermo-responsive alginate-g-P(NIPAAm) hydrogel as a vehicle for sustained and controlled gene delivery

This study was designed to produce the optimal Alg-g-P(NIPAAm) hydrogel with respect to localised delivery of DNA nanoparticles as a potential medical device for those with castrate resistant prostate cancer (CRPC). Given that CRPC typically disseminates to bone causing pain, morbidity and a plethora of skeletal related events, a copolymer based hydrogel was designed to for long term release of therapeutic DNA nanoparticles.The nanoparticles were comprised of plasmid DNA (pDNA), complexed with an amphipathic cell penetrating peptide termed RALA that is designed to enter cells with high efficiency. Alginate MW and M/G ratio affected stiffness, structure, injectability and degradation of the Alg-g-P(NIPAAm) hydrogel. Algogel 3001, had the optimal characteristics for long-term application and was loaded with RALA/pDNA NPs. From the release profiles, it was evident that RALA protected the pDNA from degradation over a 30-day period and conferred a sustained and controlled release profile from the hydrogels compared to pDNA only.Taken together, we have designed a slowly degrading hydrogel suitable for sustained delivery of nucleic acids when incorporated with the RALA delivery peptide. This now opens up several opportunities for the delivery of therapeutic pDNA from this thermo-responsive hydrogel with numerous medical applications.Graphical abstract
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research