TY - JOUR
T1 - Validation of hyaluronic acid-agar-based hydrogels as vitreous humor mimetics for in vitro drug and particle migration evaluations
AU - Thakur, Sachin S.
AU - Shenoy, Siddharth K.
AU - Suk, Jung Soo
AU - Hanes, Justin S.
AU - Rupenthal, Ilva D.
N1 - Funding Information:
This work was supported by the Buchanan Charitable Foundation, and the University of Auckland Faculty Research Development Fund. The illustration used for the eye in the graphical abstract for this manuscript was sourced from the NEI Photos and Images catalog. The near neutral particle technology described in this publication is being developed by Kala Pharmaceuticals. J.H. declares a financial, a management/advisor, and a paid consulting relationship with Kala Pharmaceuticals. J.H. is a cofounder of Kala Pharmaceuticals and owns company stock, which is subject to certain restrictions under Johns Hopkins University policy. The terms of this arrangement are being managed by Johns Hopkins University in accordance with its conflict-of-interest policies.
Funding Information:
This work was supported by the Buchanan Charitable Foundation , and the University of Auckland Faculty Research Development Fund . The illustration used for the eye in the graphical abstract for this manuscript was sourced from the NEI Photos and Images catalog.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/3
Y1 - 2020/3
N2 - Artificial vitreous humor holds immense potential for use in in vitro intravitreal drug delivery assays. In this study, we investigated rheological properties and drug or nanoparticle migration in hyaluronic acid (HA) – agar based hydrogels and compared these characteristics with bovine vitreous humor. Gel compositions identified in literature containing HA (0.7–5.0 mg/ml) and agar (0.95–4.0 mg/ml) were classified as either high (VH), medium (VM) or low (VL) polymer load. Viscoelastic behavior was evaluated using oscillatory rheology, and migration of differently sized and charged polystyrene nanoparticles (NPs) through the different gels was determined via multiple particle tracking. Comparable rheological behaviour was observed between VL and bovine vitreous. Tracking evaluations revealed that increasing particle size and gel viscosity slowed NP migration. Additionally, 100 nm anionic NPs migrated slower than neutral NPs in VL and VM, while cationic NPs were immobile in all gels. Finally, distribution and clearance of sodium fluorescein was used to model drug mobility through the gels using a custom-built eye model. Flow and angular movement only influenced drug migration in VL and VM, but not VH. Finally, VL and VM demonstrated to have the most similar sodium fluorescein clearance to that of bovine vitreous humor. Together, these evaluations demonstrate that low viscosity HA-agar gels can be used to approximate nanoparticle and drug migration through biological vitreous humor.
AB - Artificial vitreous humor holds immense potential for use in in vitro intravitreal drug delivery assays. In this study, we investigated rheological properties and drug or nanoparticle migration in hyaluronic acid (HA) – agar based hydrogels and compared these characteristics with bovine vitreous humor. Gel compositions identified in literature containing HA (0.7–5.0 mg/ml) and agar (0.95–4.0 mg/ml) were classified as either high (VH), medium (VM) or low (VL) polymer load. Viscoelastic behavior was evaluated using oscillatory rheology, and migration of differently sized and charged polystyrene nanoparticles (NPs) through the different gels was determined via multiple particle tracking. Comparable rheological behaviour was observed between VL and bovine vitreous. Tracking evaluations revealed that increasing particle size and gel viscosity slowed NP migration. Additionally, 100 nm anionic NPs migrated slower than neutral NPs in VL and VM, while cationic NPs were immobile in all gels. Finally, distribution and clearance of sodium fluorescein was used to model drug mobility through the gels using a custom-built eye model. Flow and angular movement only influenced drug migration in VL and VM, but not VH. Finally, VL and VM demonstrated to have the most similar sodium fluorescein clearance to that of bovine vitreous humor. Together, these evaluations demonstrate that low viscosity HA-agar gels can be used to approximate nanoparticle and drug migration through biological vitreous humor.
KW - In vitro model
KW - Intravitreal injection
KW - Ocular drug delivery
KW - Vitreous humor
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U2 - 10.1016/j.ejpb.2020.01.008
DO - 10.1016/j.ejpb.2020.01.008
M3 - Article
C2 - 31981693
AN - SCOPUS:85078458448
SN - 0939-6411
VL - 148
SP - 118
EP - 125
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -