title: Optimized synthesis and crystalline stability of γ-cyclodextrin metal-organic frameworks for drug adsorption.
abstract: The biocompatible and renewable cyclodextrin metal-organic frameworks (CD-MOFs) have addressed a range of opportunities in molecular storage and separation sciences. The reported protocols for their synthesis, however, were carried out at room temperature over long time periods of time (24h), producing crystals of relatively poor uniformity. In this investigation, micron sized γ-CD-MOFs were synthesized by an optimized vapor diffusion method at elevated temperature (50°C) within 6h, after which the size control, crystalline stability and drug adsorption behavior were investigated in detail. In this manner, uniform cubic γ-CD-MOF crystals were obtained when the reaction temperature was raised to 50°C with pre-addition of the reaction solvent. The size of γ-CD-MOFs was adjusted efficiently by changing the reactant concentrations, temperatures, time, γ-CD ratios to KOH and surfactant concentrations, without influencing the porosity and crystallinity of the material markedly. Varing degrees of reduction in crystallinity and change in morphology were observed when the γ-CD-MOF crystals are treated under conditions of high temperature (100°C), high humidity (92.5%) and polar solvents (e.g., MeOH and DMF). In relation to drug adsorption by γ-CD-MOFs, most of the drug molecules containing carboxyl groups showed relatively high adsorption (>5%), while low adsorption (<5%) was found for drugs with nitrogen-containing heterocyclic rings. In addition, the adsorption kinetics of captopril to standard γ-CD-MOFs matched a pseudo-second-order model rather well, whilst captopril adsorption to the damaged γ-CD-MOFs only partially matched the pseudo-second-order model. In summary, based upon the optimized synthesis and size control of γ-CD-MOFs, the crystalline stability and drug adsorption characteristics of γ-CD-MOF crystals have been evaluated as a fundamental requirement of a potential vehicle for drug delivery.
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
authors.forename: Botao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Institut de Sciences Moléculaires d'Orsay, Université Paris-Sud, Université Paris-Saclay, UMR CNRS 8214, 91405 Orsay Cedex, France.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Lv
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Vikramjeet
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: J Fraser
authors.initials: JF
authors.lastname: Stoddart
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: xuxu3426@sina.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institut de Sciences Moléculaires d'Orsay, Université Paris-Sud, Université Paris-Saclay, UMR CNRS 8214, 91405 Orsay Cedex, France. Electronic address: ruxandra.gref@u-psud.fr.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: jwzhang@simm.ac.cn.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000327:Adsorption; D016503:Drug Delivery Systems / Q000379:methods; D006358:Hot Temperature; D008670:Metals / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D012997:Solvents / Q000737:chemistry; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D008670:Metals; D009942:Organometallic Compounds; D012997:Solvents; D047408:gamma-Cyclodextrins; C023792:gamma-cyclodextrin
keywords: Crystalline stability; Cyclodextrin-metal-organic frameworks; Drug adsorption; Synthesis