Freeze-drying of monoclonal antibody-conjugated gold nanorods: Colloidal stability and biological activity

[Display omitted] Maintaining colloidal stability of nanoparticles in suspensions is a major challenge. Therefore, freeze-drying (lyophilization) is recently proposed to preserve colloidal stability of nanoparticles through maintaining them in a solid state. However, freeze-drying would itself induc...

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Bibliographic Details
Published in:International journal of pharmaceutics 2018-10, Vol.550 (1-2), p.269-277
Main Authors: Hamaly, Majd A., Abulateefeh, Samer R., Al-Qaoud, Khaled M., Alkilany, Alaaldin M.
Format: Article
Language:English
Subjects:
Antibodies
Antigens, CD20 - metabolism
Colloids
Cryoprotective Agents - chemistry
Drug Stability
Freeze Drying
Gold - administration & dosage
Gold - chemistry
Gold nanoparticles
Humans
Lymphoma, B-Cell - metabolism
Lyophilization
Mannitol - chemistry
Nanotubes - chemistry
Rituximab
Rituximab - administration & dosage
Rituximab - chemistry
Trehalose - chemistry
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Summary:[Display omitted] Maintaining colloidal stability of nanoparticles in suspensions is a major challenge. Therefore, freeze-drying (lyophilization) is recently proposed to preserve colloidal stability of nanoparticles through maintaining them in a solid state. However, freeze-drying would itself induce nanoparticle aggregation unless proper formulation with a careful selection of cryoprotectants is considered. Herein, we evaluate the colloidal stability of gold nanorods (GNRs) conjugated with a rituximab as a model monoclonal antibody upon freeze-drying in the presence of various cryoprotectants (mannitol, trehalose and sucrose). Aggregation-induced optical responses of GNRs were used as a sensitive tool to follow nanoparticle aggregation. In the absence of cryoprotectants, rituximab-conjugated GNRs aggregate irreversibly while evaluated cryoprotectants exhibit a significant protective effect. Maximal colloidal stability of GNRs is observed in the presence of trehalose while mannitol results in best cake formation in terms of shape and integrity. A combination of trehalose and mannitol produces a lyophilized product with satisfactory GNR colloidal stability and cake shape. Moreover, we show that freeze-dried rituximab-conjugated GNRs in presence of proper cryoprotectants maintain typical binding to lymphoma tissues as confirmed via immunohistochemistry assay.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2018.08.045