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Y.-S. Hwang, C.-H. Wang, Y.-S. Chiang, G.-H. Hsiue, C.-C. Lai; A Novel Thermo-Sensitive, Biodegradable and Biocompatible Hydrogel as a Carrier for Bevacizumab. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5301.
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The protein drugs biologics have been widely used in the clinical therapeutics and have high effectiveness. Short half-life in vivo, however, is the limitation of current clinical application. Long-term slow-release design of the biologics is the ideal of delivery. However, the biologics are easily denatured if through a high temperature or acid/base process. We design a novel hydrogel which could pack the biologics and slowly release the biologics from inside.
A novel biodegradable and thermo-sensitive block copolymers consisting of poly(2-ethyl-2-oxzoline) and poly(ε-caprolactone) (PEOz-PCL-PEOz, ECE) were synthesized. The triblock copolymers have a reversible sol (room temperature)-gel (physiological temperature) phase transition, which can facilitate an easy encapsulation of the fragile biologics. The slow ECE biodegradation can also be utilized for a purpose of slow drug release.
The synthesized ECE hydrogel was chemically and molecularly characterized by 1H NMR and FTIR, respectively. Its in vitro degradation rate was studied in balanced salt solution by gel permeation chromatography (GPC). The result showed almost no changes in the molecular weight of ECE in 2 months. Scanning electron microscope (SEM) was utilized to assessing the porosity formation. Additionally, little or no in vitro cytotoxic effects of ECE were obtained from human retinal pigment epithelial (RPE) cell line co-cultured with a medium mixed with ECE. The in vitro and in vivo drug release of bevacizumab, which is a currently used antibody drug for anti-vascular endothelial growth factor (anti-VEGF), encapsulated by ECE was linearly sustained in the first 2 months. Retinal photography and electrophysiology of rabbit eyes after intravitreal injection of ECE further demonstrated the good in vivo biocompatibility. The electroretinogram showed comparable a and b waveforms between the study and control eyes in the first 2 months after intravitreal injection. Histology of the rabbit eyes demonstrated no morphologic change of the neuroretinal tissue.
A phase-transition, low in vitro/in vivo noncytotoxicity, biodegradability and good intraocular biocompatibility make the ECE hydrogel a great potential for biomedical and therapeutic applications.
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