Carboxymethyl cyclosophoraoses as a flexible pH-responsive solubilizer for pindolol

Yiluo Hu; Hwanhee Kim; Vijay Vilas Shinde; Daham Jeong; Youngjin Choi; Eunae Cho; Seunho Jung

doi:10.1016/j.carbpol.2017.08.026

Carboxymethyl cyclosophoraoses as a flexible pH-responsive solubilizer for pindolol

Carbohydr Polym. 2017 Nov 1:175:493-501. doi: 10.1016/j.carbpol.2017.08.026. Epub 2017 Aug 9.

Authors

Yiluo Hu¹, Hwanhee Kim¹, Vijay Vilas Shinde¹, Daham Jeong¹, Youngjin Choi², Eunae Cho³, Seunho Jung⁴

Affiliations

¹ Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea.
² Departments of Food Science and Technology, BioChip Research Center, Hoseo University, Chungcheongnam-do, South Korea.
³ Center for Biotechnology Research in UBITA (CBRU), Institute for Ubiquitous Information Technology and Applications (UBITA), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea. Electronic address: echo@konkuk.ac.kr.
⁴ Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea. Electronic address: shjung@konkuk.ac.kr.

PMID: 28917893
DOI: 10.1016/j.carbpol.2017.08.026

Abstract

In the present study, cyclosophoraoses (CyS) (β-1,2 linked cyclic glucans, with glucopyranose units ranging from 17 to 23) isolated from Rhizobium leguminosarum biovar viciae VF-39 were modified with carboxymethyl (CM) groups, and the pH-sensitive complexation of CM CyS with pindolol was investigated. The solubility of pindolol increased 32-fold by its complexation with 5mM CM CyS at pH 10, whereas it shows no significant change at pH 3. Pindolol, a β-adrenergic blocking agent, has a hydrophobic nature at non-ionized state, and CM CyS could solubilize efficiently pindolol in a high alkaline solution. The carboxymethylation of flexible CyS allows them to present a more suitable cavity for the hydrophobic pindolol at pH 10, which is differentiated from CM β-cyclodextrin (β-CD). It can be interpreted as that the anionic repulsion effectively modulates the flexible and distorted conformation of CyS rather than rigid annular shape of β-CD. Resultingly, the highly solubilized CM CyS/pindolol complex was characterized by UV-vis, T1 relaxation, ROESY, DOSY NMR spectroscopy, FT-IR spectroscopy, SEM, and molecular modeling studies. The antioxidant activity of pindolol was also improved 260% in the complex compared to free pindolol. The use of flexible host molecules with pH-responsive substituents would be applied in the development of smart systems for sensing or in biomedical fields.

Keywords: Carboxymethyl cyclosophoraoses; Host-guest complexation; Pindolol; Solubilization; pH-responsive.