title: Colloidal stability of citrate and mercaptoacetic acid capped gold nanoparticles upon lyophilization: effect of capping ligand attachment and type of cryoprotectants.
abstract: For various applications of gold nanotechnology, long-term nanoparticle stability in solution is a major challenge. Lyophilization (freeze-drying) is a widely used process to convert labile protein and various colloidal systems into powder for improved long-term stability. However, the lyophilization process itself may induce various stresses resulting in nanoparticle aggregation. Despite a plethora of studies evaluating lyophilization of proteins, liposomes, and polymeric nanoparticles, little is known about the stability of gold nanoparticles (GNPs) upon lyophilization. Herein, the effects of lyophilization and freeze-thaw cycles on the stability of two types of GNPs: Citrate-capped GNPs (stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic acid, MAA-GNPs) are investigated. Both types of GNPs have similar core size and effective surface charge as evident from transmission electron microscopy and zeta potential measurements, respectively. Plasmon absorption of GNPs and its dependence on nanoparticle aggregation was employed to follow stability of GNPs in combination with dynamic light scattering analysis. Plasmon peak broadening index (PPBI) is proposed herein for the first time to quantify GNPs aggregation using nonlinear Gaussian fitting of GNPs UV-vis spectra. Our results indicate that Cit-GNPs aggregate irreversibly upon freeze-thaw cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable stability under the same conditions. Cit-GNPs exhibit no significant aggregation in the presence of cryoprotectants (molecules that are typically used to protect labile ingredients during lyophilization) upon freeze-thaw cycles and lyophilization. The effectiveness of the cyroprotectants evaluated was on the order of trehalose or sucrose > sorbitol > mannitol. The ability of cryoprotectants to prevent GNPs aggregation was dependent on their chemical structure and their ability to interact with the GNPs as assessed with zeta potential analysis.
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan , Amman 11942, Jordan.
authors.forename: Alaaldin M
authors.initials: AM
authors.lastname: Alkilany
authors.forename: Samer R
authors.initials: SR
authors.lastname: Abulateefeh
authors.forename: Kayla K
authors.initials: KK
authors.lastname: Mills
authors.forename: Alaa I Bani
authors.initials: AI
authors.lastname: Yaseen
authors.forename: Majd A
authors.initials: MA
authors.lastname: Hamaly
authors.forename: Hatim S
authors.initials: HS
authors.lastname: Alkhatib
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Aiedeh
authors.forename: John W
authors.initials: JW
authors.lastname: Stone
mesh_terms: D019343:Citric Acid / Q000737:chemistry*; D003102:Colloids; D003451:Cryoprotective Agents / Q000737:chemistry*; D005612:Freeze Drying; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D013864:Thioglycolates / Q000737:chemistry*
chemical_list: D003102:Colloids; D003451:Cryoprotective Agents; D013864:Thioglycolates; D019343:Citric Acid; D006046:Gold; C017487:2-mercaptoacetate