Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs

• Published in: Advanced healthcare materials 2018-05, Vol.7 (9), p.e1701393-n/a
• Main Authors: Li, Jianyu, Weber, Eckhard, Guth‐Gundel, Sabine, Schuleit, Michael, Kuttler, Andreas, Halleux, Christine, Accart, Nathalie, Doelemeyer, Arno, Basler, Anne, Tigani, Bruno, Wuersch, Kuno, Fornaro, Mara, Kneissel, Michaela, Stafford, Alexander, Freedman, Benjamin R., Mooney, David J.
• Format: Article
• Language: English
• Subjects: Achilles tendon; Achilles Tendon - metabolism; Achilles Tendon - pathology; Active control; Animals; Biocompatibility; Biodegradation; biological drugs; Biological products; Biomimetic Materials - chemistry; Biomimetic Materials - pharmacokinetics; Biomimetic Materials - pharmacology; Clay; composite hydrogels; Control stability; controlled delivery; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drug delivery; Drug delivery systems; Drug development; Drugs; Feasibility studies; Female; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Insulin; Insulin-Like Growth Factor I; Mice; Microparticles; Nanoparticles; NIH 3T3 Cells; Peptides - chemistry; Peptides - pharmacokinetics; Peptides - pharmacology; Rats; Rats, Sprague-Dawley; Regenerative medicine; Shelf life; Storage stability; Tendon Injuries - drug therapy; Tendon Injuries - metabolism; Tendon Injuries - pathology; Tissue engineering; tough hydrogels
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201701393

Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin‐like growth factor‐1 mimetic protein (8 mg mL−1) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine. This work reports biocompatible composite hydrogels with high loading and extremely extended, localized release of biological drugs. The hydrogels demonstrate high mechanical toughness (sustain >80% compressive strains), large drug loading capacity (8 mg mL−1), extended release duration (28 d), and highly localized drug release (the ratio of tissue‐ and serum‐level of the drug >10 000).