April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Development of injectable hydrogel based on catalyst-free click chemistry for controlled release of macromolecules - a formulation study for Avastin
Author Affiliations & Notes
  • Yu Yu
    Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science & Technology, Hong Kong, China
    Division of Biomedical Engineering, The Hong Kong University of Science & Technology, Hong Kong, China
  • Ying Chau
    Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science & Technology, Hong Kong, China
    Division of Biomedical Engineering, The Hong Kong University of Science & Technology, Hong Kong, China
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 474. doi:
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      Yu Yu, Ying Chau; Development of injectable hydrogel based on catalyst-free click chemistry for controlled release of macromolecules - a formulation study for Avastin. Invest. Ophthalmol. Vis. Sci. 2014;55(13):474.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

We aim to formulate an in situ hydrogel based on catalyst-free click-chemistry for intravitreal release of ocular therapeutics with tunable rate and extended duration.

 
Methods
 

Hyaluronan (HA) was chosen as the main hydrogel component for its biocompatibility and degradability in vitreous. Vinylsulfonate HA (HA-VS), thiolated HA (HA-SH) and thiolated dextran (Dex-SH) of various degrees of modification (DM) and concentrations were prepared according to methods developed in our lab (Yu and Chau, 2012). HA-VS, Avastin and SH polymer solutions were mixed to form drug-loaded hydrogels at physiological conditions. Gel formation was confirmed by dynamic mechanical measurement. Hydrogels were placed in phosphate-buffered saline for release experiments, and released Avastin was detected using Bradford assay.Effects of gel formation and incubation on cell viability were assessed with ARPE-19 cells.

 
Results
 

The formed gel was transparent. The burst release of drug was reduced by increasing polymer concentration (fig 1A). We controlled the DM to minimize the mesh size while minimizing excess VS groups, which cause undesirable protein binding. Excess VS groups were further masked by using SH polymer at 2:1 mass ratio to HA-VS (fig 1B). Selected formulations were allowed short lapse time (5 minutes) after mixing before release experiments to mimic in intravitreal gelation. Because of the fast gelation kinetics(<20 seconds, data not shown), they did not display burst release and showed prolonged release with adjustable rate of drug for at least 3 months (figure 1C).Both the gelation process and the well-formed hydrogel were compatible to ARPE-19 cells (fig 2).

 
Conclusions
 

The tunable release rate, fast gelation, long release time (>3 months) and biocompatibility made the gel system a suitable platform for formulating macromolecules for ocular therapy of chronic diseases.

 
 
Gel formulation for A: controlling the burst release; B: avoiding undesirable protein binding; C: short gelation time and prolonged release for 3 months.
 
Gel formulation for A: controlling the burst release; B: avoiding undesirable protein binding; C: short gelation time and prolonged release for 3 months.
 
 
Live/Dead assay images of ARPE-19 cells after A: incubation with well-formed gels; and B: exposure to gel formation. Green represents live cells.
 
Live/Dead assay images of ARPE-19 cells after A: incubation with well-formed gels; and B: exposure to gel formation. Green represents live cells.
 
Keywords: 412 age-related macular degeneration  
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