April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
A Novel Thermo-Sensitive, Biodegradable and Biocompatible Hydrogel as a Carrier for Bevacizumab
Author Affiliations & Notes
  • Y.-S. Hwang
    Dept of Ophthalmology, Chang Gung Memorial Hosp-Linko, Taoyuan County, Taiwan
  • C.-H. Wang
    Polymer Technology Division, Material and Chemical Research Laboratories, Chang Gung Memorial Hosp-Linko, Industrial Technology Research Institute/Hsinchu, Taiwan
  • Y.-S. Chiang
    Department of Chemical Engineering, National Tsing Hua University, HsinChu County, Taiwan
  • G.-H. Hsiue
    Department of Chemical Engineering, National Tsing Hua University, HsinChu County, Taiwan
  • C.-C. Lai
    Dept of Ophthalmology, Chang Gung Memorial Hosp-Linko, Taoyuan County, Taiwan
  • Footnotes
    Commercial Relationships  Y.-S. Hwang, None; C.-H. Wang, None; Y.-S. Chiang, None; G.-H. Hsiue, None; C.-C. Lai, None.
  • Footnotes
    Support  CMRP Grant 380181
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5301. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: drug toxicity/drug effects • age-related macular degeneration 
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