Amination degree of gelatin is critical for establishing structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems

• Published in: Materials Science & Engineering C Vol. 98; pp. 897 - 909
• Main Authors: Luo, Li-Jyuan, Lai, Jui-Yang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2019; Elsevier BV
• Subjects: Adipic acid dihydrazide; Amination; Animals; Biocompatible Materials - chemistry; Biodegradability; Biodegradable thermogel; Biodegradation; Biomaterial amination; Biomaterials; Biomedical materials; Biopolymers; Calorimetry, Differential Scanning; Carbodiimide; Chemical synthesis; Copolymer synthesis; Copolymers; Cytotoxicity; Drug delivery; Drug Delivery Systems; Electron microscopy; Gelatin; Gelatin - chemistry; Gelatin - ultrastructure; Gelation; Gels - chemistry; Glaucoma; Graft copolymers; Intracameral drug delivery; Isopropylacrylamide; Long-acting injectable depot system; Materials science; Organic chemistry; Oxidative stress; Pharmacology; Pilocarpine; Poly(N-isopropylacrylamide); Proteins; Proton Magnetic Resonance Spectroscopy; Rabbits; Signs and symptoms; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Structure-function relationships; Ultrastructure; Intracameral drug delivery; Long-acting injectable depot system; Biodegradable thermogel; Biomaterial amination; Copolymer synthesis
• DOI: 10.1016/j.msec.2019.01.051
• ISSN: 0928-4931; 1873-0191

Glaucoma is a lifelong disorder that necessitates continuous medical therapy to manage its symptoms and preserve the vision of patients; accordingly, it is highly beneficial to develop a long-acting injectable depot system that can exhibit better drug delivery capability. This study aims to investigate the effect of the amination degree of gelatin on the carbodiimide-mediated grafting of thermo-responsive poly(N-isopropylacrylamide) segments onto biodegradable protein backbone molecules. Moreover, the potential applications of these carrier materials for intracameral pilocarpine administration in glaucomatous subjects will be considered. The gelatins with different amination degrees that are prepared by controlling the feed amount of adipic acid dihydrazide are further used for the synthesis of graft copolymers. The results of chemical characterization and electron microscopy studies showed that both grafting reaction effectiveness and gelling carrier ultrastructure vary in response to biomaterial amination. Compared to unmodified biopolymer thermogel without gel formation, graft copolymers that are composed of aminated gelatin networks showed a more remarkable temperature-triggered pilocarpine capture under physiological conditions. This could create more stable depot-forming carrier systems with improved in vivo pharmacological efficacy. Although the increase in amination degree enhances the biodegradation resistance of graft copolymers for achieving extended drug release profiles and provides significant therapeutic benefits, carriers with excess positive charges may potentiate the cytotoxic actions of oxidative stress signals and may cause damage in cellular barrier integrity. Consequently, unfavorable ocular tissue responses and poor treatment outcomes are observed in glaucomatous rabbits. For the first time, our findings suggest that the amination degree of gelatin performs a crucial function in guiding the development of structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems. [Display omitted] •We examine role of biomaterial amination in development of biodegradable thermogel.•A series of aminated gelatin networks are grafted with carboxyl-terminated PNIPAAm.•Amine-modification of biopolymer backbones is critical for synthesis of copolymers.•Amination degree mediates structure-property-function relationship of drug carrier.•Intracameral depot formulations of pilocarpine need an optimal level of amination.