title: Solubilization of haloperidol by acyclic succinoglycan oligosaccharides.
abstract: The isolated succinoglycan octasaccharide dimers isolated from Sinorhizobium meliloti 1021 have unique acyclic structures, displaying amphipathic properties against water. Thus, their potential usage as solubilizers of various water-insoluble drugs through non-covalent complexation are possible. In this study, we examined the solubility of a poorly water-soluble drug, haloperidol, in the presence of the acyclic form of succinoglycan dimers, and demonstrated that its solubility was increased up to 87 fold, Interestingly, the level of its solubility was even 7-10 fold higher than that achieved with β cyclodextrin or its derivatives that are cyclic forms, which is possibly due to the molecular flexibility of the acyclic structure of the dimers as well as the hydrophobic nature. Analyses of the stoichiometry and the stability constants for each complex were performed using phase solubility method, respectively. Additional analyses were also performed to confirm the formation of succinoglycan-drug complexes. Furthermore hypothetical 3-dimesional conformation of the complex was estimated through molecular docking simulations. Upon cytotoxicity test with a human cell line, the succinoglycan dimers displayed little effect up to 1000 μM, suggesting their potential usage to improve solubility and bioavailability of poorly soluble therapeutic agents.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Hwanhee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Cho
authors.affiliation: BioChip Research Center, Hoseo University, Asan 336-795, South Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Biological Science & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Im Soon
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea; Department of Biological Science & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Seunho
authors.initials: S
authors.lastname: Jung
mesh_terms: D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D057809:HEK293 Cells; D006220:Haloperidol / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000494:pharmacology; D016962:Sinorhizobium meliloti; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; C056779:succinoglycan; D006220:Haloperidol