Elsevier

Carbohydrate Polymers

Volume 95, Issue 1, 5 June 2013, Pages 366-370
Carbohydrate Polymers

Investigation of water-soluble inclusion complex of hypericin with β-cyclodextrin polymer

https://doi.org/10.1016/j.carbpol.2013.03.020Get rights and content

Highlights

  • The water solubility of HY was improved by complexation with CDP.

  • The mole ratio of β-CD unit to HY was determined as 2:1.

  • It provided an approach for a more rational pharmaceutical application of HY.

Abstract

A water-soluble inclusion complex of hypericin (HY) with β-cyclodextrin polymer (CDP) was achieved by supramolecular interactions between HY and CDP. The inclusion complex (HY-CDP) was characterized by 1H NMR, FTIR, and UV–vis spectroscopies. Compared with HY, the water-solubility of HY-CDP was greatly enhanced because of the water-soluble CDP host. The mole ratio of β-cyclodextrin (β-CD) unit in CDP to HY was determined as 2:1. At 25 °C, the dissociated constant of HY-CDP was measured as 1.47 × 10−7 mol L−1 by UV–vis spectroscopy. In the formation of inclusion complexes, CDP could overcome the β-CD drawbacks – such as the poor water-solubility and the restriction of single cavity size, indicating it was able to use as a universal solubilizer for pharmaceutical application.

Introduction

β-Cyclodextrin (β-CD) is cyclic oligosaccharides including glucose unites linked by α-1,4-glucosidic bonds. Given the hydrophobic internal cavity and hydrophilic external surface, it can form supramolecular host–guest complexes with a variety of hydrophobic molecules (Szejtli, 1998). Through the distinct physical and chemical properties, β-CD is used in many fields, such as electroanalysis (Chen, Zhang, Jiang, & Diao, 2011), biotechnology (Yang, Lin, Chen, & Liu, 2009), environmental protection (Zhang, Chen, Zha, & Diao, 2012), and foodstuff (Hu et al., 2012b, Hu et al., 2012a). β-CD appears to be the best natural cyclodextrin for pharmaceutical applications because of its efficient drug complexation (Hu et al., 2012b, Hu et al., 2012a), however, some limitations exist for the applications of β-CD: (1) the aqueous solubility of β-CD is low. (2) Although some chemical modifications have been prepared to improve the aqueous solubility of β-CD, adopted chemical routes usually use the toxic organic reagent. (3) Only several organic molecules having specific sizes can form inclusion complexes with CDs and the single and small size of CD cavities limit the CD use in pharmaceutical applications. β-Cyclodextrin polymer (CDP) has been obtained by reaction of the parent β-CD with a cross-linking agent, epichlorohydrin (EP) (Renard, Deratani, Volet, & Sebille, 1997). Especially, CDP as a highly water-soluble polymer is well known to selectively form inclusion complexes. Moreover, the features of CDP have been widely exploited, e.g., for solubilization and pharmaceutics (Li et al., 2004, Zhang et al., 2011, Zhao et al., 2009).

Hypericin (HY) is a natural polycyclic quinone from Hypericum perforatum, commonly known as St John's wort (Agostinis, Vantieghem, Merlevede, & de Witte, 2002). The chemical structure of HY is shown in Fig. 1(a). This natural product is an effective antidepressant and anxiolytic (Lavie et al., 1995, Vandenbogaerde et al., 2000), an antiretroviral agent (Lavie et al., 1995), and a potent photosensitizer suggested for use in photodynamic therapy of cancer (Saw, Olivo, Soo, & Heng, 2006). However, HY is very lipophilic and water-insoluble, which makes intravenous injection problematic and restrains its medical applications.

Up to date, only a few studies focus on cyclodextrins and HY (de los Reyes and Koda, 2001, Falk et al., 1998, Sattler et al., 1997, Vandenbogaerde et al., 2000), but the water-solubility of HY is not remarkably improved with CDs and the host–guest interaction of HY with CDs is not explored carefully. In this paper, we used CDP as a solubilizing agent for HY, and studied the formation of a water-soluble inclusion complex between HY and CDP. In this preparation of HY-CDP, there was not any chemical synthesis in order to preserve the original structure of HY. The method would provide a convenient and efficient approach for obtaining HY with high water solubility, high bioavailability and low toxicity.

Section snippets

Experimental

HY was purchased from Aldrich. β-CD, epichlorohydrin (EP), ethylene glycol, and other reagents were all analytical purity and purchased from Sinopharm Chemical Reagents Company. Double distilled and sterilized water was used to prepare all solution.

Characterization of HY-CDP

Fig. 2 shows the FTIR spectra of (a) HY, (b) CDP, and (c) HY-CDP. The typical IR spectrum of HY was presented in Fig. 2(a), which was in good agreement with literature (Kapinus, Falk, & Tran, 1999). The carbonyl and aromatic stretching vibrations at 1595 cm−1 was exhibited in Fig. 2(a). Fig. 2(b) shows the typical CDP absorptions, such as the coupled Csingle bondOsingle bondC stretching vibrations at ~1160 cm−1, the coupled Csingle bondO/Csingle bondC stretching vibrations at ~1030 cm−1, CH2 stretching vibrations at ~2920 cm−1, CH bending

Conclusion

In the present work, the water-soluble host, CDP improved the physical and chemical properties of the HY guest by forming HY-CDP inclusion complex. This work involved the characterization of HY-CDP, aiming to gain high solubility, and stable electro-activity in water. The inclusion complex between HY and β-CD unit in CDP was formed with a stoichiometry of 1:2 and the dissociated constant KD was obtained by UV–vis spectroscopy. All the results suggested that the CDP complexation technique was a

Acknowledgments

The authors acknowledged the financial support from the National Natural Science Foundation of China (Grant Nos. 21273195, 20973151, 20901065), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Foundation of the Educational Committee of Jiangsu Provincial General Universities Graduate Student Scientific Research Invention Plan, and the Foundation of Jiangsu Provincial Key Program of Physical Chemistry in Yangzhou University.

References (29)

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