Development of Nanosilicate-Hydrogel Composites for Sustained Delivery of Charged Biopharmaceutics.

Abstract

Nanocomposite hydrogels containing two-dimensional nanosilicates (NS) have emerged as a new technology for the prolonged delivery of biopharmaceuticals. However, little is known about the physical-chemical properties governing the interaction between NS and proteins and the release profiles of NS-protein complexes in comparison to traditional poly(ethylene glycol) (PEG) hydrogel technologies. To fill this gap in knowledge, we fabricated a nanocomposite hydrogel composed of PEG and laponite and identified simple but effective experimental conditions to obtain sustained protein release, up to 23 times slower as compared to traditional PEG hydrogels, as determined by bulk release experiments and fluorescence correlation spectroscopy. Slowed protein release was attributed to the formation of NS-protein complexes, as NS-protein complex size was inversely correlated with protein diffusivity and release rates. While protein electrostatics, protein concentration, and incubation time were important variables to control protein-NS complex formation, we found that one of the most significant and less appreciated variable to obtain a sustained release of bioactive proteins was the buffer chosen for preparing the initial suspension of NS particles. The buffer was found to control the size of nanoparticles, the absorption potential, morphology, and stiffness of hydrogels. From these studies, we conclude that the PEG-laponite composite fabricated is a promising new platform for sustained delivery of positively charged protein therapeutics.