Injectable hydrogels based on the hyaluronic acid and poly (γ-glutamic acid) for controlled protein delivery

• Published in: Carbohydrate polymers 2018-01, Vol.179, p.100-109
• Main Authors: Ma, Xuebin, Xu, Tingting, Chen, Wei, Qin, Hongye, Chi, Bo, Ye, Zhiwen
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Animals; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Cell Survival - drug effects; Drug Delivery Systems; Elasticity; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogels - chemical synthesis; Hydrogels - chemistry; Hydrogels - pharmacology; Injectable hydrogel; Injections; Mice; NIH 3T3 Cells; Poly (γ-glutamic acid); Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemistry; Protein delivery; Rheology; Serum Albumin, Bovine - chemistry; Shear Strength; Viscosity
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2017.09.071

•HA/γ-PGA hydrogels can be formed in situ as fast as 9s.•HA/γ-PGA hydrogels exhibit good mechanical properties and superior biocompatible.•Gelation time, protein release behavior can be modulated easily.•HA/γ-PGA hydrogels are a promising candidate as protein carrier. Injectable hydrogels have great potential in minimally invasive delivery. In this work, novel injectable hydrogels were prepared via self-crosslinking of aldehyde hyaluronic acid (HA-CHO) and hydrazide-modified poly (γ-glutamic acid) (γ-PGA-ADH) for proteins delivery. The HA/γ-PGA hydrogels could be formed in situ as fast as 9s with high swelling ratios. Rheological properties illustrated a wide processing range and good mechanical properties, which were reflected by broad linear viscoelastic region and higher threshold shear stress (σc) and storage modulus (G′). Meanwhile, the gelation time, swelling ratio, rheological properties, as well as the protein release behavior could be modulated conveniently. Bovine serum albumin (BSA) was designed as a model drug to study the release behavior. We found that the release mechanisms were either diffusion or Case-II relaxation depending on the different hydrogel components. The HA/γ-PGA hydrogels also showed good biocompatibility. Therefore, the HA/γ-PGA hydrogels have great potential as promising injectable biomaterials for controlled protein delivery.