Study in vivo intraocular biocompatibility of in situ gelation hydrogels: poly(2-ethyl oxazoline)-block-poly(ε-caprolactone)-block-poly(2-ethyl oxazoline) copolymer, matrigel and pluronic F127

• Published in: PloS one 2013-07, Vol.8 (7), p.e67495
• Main Authors: Hwang, Yih-Shiou, Chiang, Ping-Ray, Hong, Wei-Hsin, Chiao, Chuan-Chin, Chu, I-Ming, Hsiue, Ging-Ho, Shen, Chia-Rui
• Format: Article
• Language: English
• Subjects: Animals; Biocompatibility; Biocompatible Materials - administration & dosage; Biocompatible Materials - chemistry; Biocompatible Materials - toxicity; Biodegradation; Biology; Biomedical materials; Block copolymers; Carriers; Cell culture; Chemical engineering; Chemistry; Collagen - administration & dosage; Collagen - chemistry; Collagen - toxicity; Controlled release; Cytotoxicity; Diabetic retinopathy; Drug carriers; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - toxicity; Drug Combinations; Drug delivery; Drug delivery systems; Drug development; Drugs; Electrophysiology; Extracellular matrix; Female; Gelation; Histology; Hydrogels; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - toxicity; In vivo methods and tests; Laboratories; Laminin - administration & dosage; Laminin - chemistry; Laminin - toxicity; Macular degeneration; Materials Science; Media (culture); Medicine; Phase transitions; Photography; Poloxamer - administration & dosage; Poloxamer - chemistry; Poloxamer - toxicity; Poloxamers; Polyamines - administration & dosage; Polyamines - chemistry; Polyamines - toxicity; Polycaprolactone; Polyesters - administration & dosage; Polyesters - chemistry; Polyesters - toxicity; Polyethyloxazoline; Proteoglycans - administration & dosage; Proteoglycans - chemistry; Proteoglycans - toxicity; Rabbits; Retina - drug effects; Retina - pathology; Stem cells; Sustained release; Therapeutic applications; Thermosensitive; Tissue engineering; Toxicity; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067495

The long term in vivo biocompatibility is an essential feature for the design and development of sustained drug release carriers. In the recent intraocular drug delivery studies, hydrogels were suggested as sustained release carriers. The biocompatibility test for these hydrogels, however, was commonly performed only through in vitro cell culture examination, which is insufficient before the clinical applications. We compared three thermosensitive hydrogels that have been suggested as the carriers for drugs by their gel-solution phase-change properties. A new block terpolymer (PEOz-PCL-PEOz, ECE) and two commercial products (Matrigel® and Pluronic F127) were studied. The results demonstrated that the ocular media remained translucent for ECE and Pluronic F127 in the first 2 weeks, but cataract formation for Matrigel occurred in 2 weeks and for Pluronic F127 in 1 month, while turbid media was observed for both Matrigel and Pluronic F127 in 2 months. The electrophysiology examinations showed significant neuroretinal toxicity of Matrigel and Pluronic F127 but good biocompatibility of ECE. The neuroretinal toxicity of Matrigel and Pluronic F127 and superior biocompatibility of ECE hydrogel suggests ECE as more appropriate biomaterial for use in research and potentially in intraocular application.