TY - JOUR
T1 - Effects of enzymatic degradation on dynamic mechanical properties of the vitreous and intravitreal nanoparticle mobility
AU - Huang, Di
AU - Chen, Ying Shan
AU - Xu, Qingguo
AU - Hanes, Justin
AU - Rupenthal, Ilva D.
N1 - Funding Information:
The authors would like to thank the Health Research Council of New Zealand [ 14/018 ] and the Buchanan Charitable Foundation for their financial support.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/6/15
Y1 - 2018/6/15
N2 - Intravitreal mobility of nanocarriers may have implications on the efficacy of the encapsulated drug in the treatment of vitreo-retinal diseases, with any changes in the integrity of the vitreous microstructure influencing nanoparticle biodistribution. This study investigated enzymatically digested vitreous models to mimic the aging eye. Collagenase, hyaluronidase, or trypsin was employed to selectively digest the structural components of the vitreous. Physical properties of digested bovine vitreous were initially assessed via texture analysis and oscillatory shear testing. Morphological changes in bovine vitreous microstructure were visualized by scanning electron microscopy and diffusion dynamics of hyaluronic acid coated nanoparticles through degraded porcine and bovine vitreous were examined using fluorescence spectroscopy and multiple particle tracking microscopy, respectively. After enzymatic treatment, the vitreous liquefied and its dynamic mechanical properties significantly changed with a decrease in stiffness and an increase in damping capacity. Micrographs confirmed specific digestion of each of the structural vitreous components. Furthermore, enzymatic degradation reduced steric hindrance and enhanced convective flow within the vitreous, resulting in increased intravitreal nanoparticle mobility which could alter the drug pharmacokinetics.
AB - Intravitreal mobility of nanocarriers may have implications on the efficacy of the encapsulated drug in the treatment of vitreo-retinal diseases, with any changes in the integrity of the vitreous microstructure influencing nanoparticle biodistribution. This study investigated enzymatically digested vitreous models to mimic the aging eye. Collagenase, hyaluronidase, or trypsin was employed to selectively digest the structural components of the vitreous. Physical properties of digested bovine vitreous were initially assessed via texture analysis and oscillatory shear testing. Morphological changes in bovine vitreous microstructure were visualized by scanning electron microscopy and diffusion dynamics of hyaluronic acid coated nanoparticles through degraded porcine and bovine vitreous were examined using fluorescence spectroscopy and multiple particle tracking microscopy, respectively. After enzymatic treatment, the vitreous liquefied and its dynamic mechanical properties significantly changed with a decrease in stiffness and an increase in damping capacity. Micrographs confirmed specific digestion of each of the structural vitreous components. Furthermore, enzymatic degradation reduced steric hindrance and enhanced convective flow within the vitreous, resulting in increased intravitreal nanoparticle mobility which could alter the drug pharmacokinetics.
KW - Dynamic mechanical properties
KW - Enzymatic degradation
KW - Intravitreal nanoparticle mobility
KW - Ocular drug delivery
KW - Vitreous liquefaction
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U2 - 10.1016/j.ejps.2018.03.023
DO - 10.1016/j.ejps.2018.03.023
M3 - Article
C2 - 29574081
AN - SCOPUS:85044579561
SN - 0928-0987
VL - 118
SP - 124
EP - 133
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
ER -