Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.

Leena Hanski; Natalja Genina; Hanna Uvell; Kristina Malinovskaja; Asa Gylfe; Timo Laaksonen; Ruzica Kolakovic; Ermei Mäkilä; Jarno Salonen; Jouni Hirvonen; Mikael Elofsson; Niklas Sandler; Pia M Vuorela

doi:10.1371/journal.pone.0115115

Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.

Leena Hanski, Natalja Genina, Hanna Uvell, Kristina Malinovskaja, Asa Gylfe, Timo Laaksonen, Ruzica Kolakovic, Ermei Mäkilä, Jarno Salonen, Jouni Hirvonen, Mikael Elofsson, Niklas Sandler, Pia M Vuorela

17 Citations (Scopus)

Abstract

Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.

Original language	English
Journal	PLOS ONE
Volume	9
Issue number	12
Pages (from-to)	e115115
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0115115
Publication status	Published - 16 Dec 2014

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Hanski, L., Genina, N., Uvell, H., Malinovskaja, K., Gylfe, A., Laaksonen, T., Kolakovic, R., Mäkilä, E., Salonen, J., Hirvonen, J., Elofsson, M., Sandler, N., & Vuorela, P. M. (2014). Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation. PLOS ONE, 9(12), e115115. https://doi.org/10.1371/journal.pone.0115115

Hanski, L, Genina, N, Uvell, H, Malinovskaja, K, Gylfe, A, Laaksonen, T, Kolakovic, R, Mäkilä, E, Salonen, J, Hirvonen, J, Elofsson, M, Sandler, N & Vuorela, PM 2014, 'Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.', PLOS ONE, vol. 9, no. 12, pp. e115115. https://doi.org/10.1371/journal.pone.0115115

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title = "Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.",

abstract = "Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.",

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AU - Genina, Natalja

AU - Uvell, Hanna

AU - Malinovskaja, Kristina

AU - Gylfe, Asa

AU - Laaksonen, Timo

AU - Kolakovic, Ruzica

AU - Mäkilä, Ermei

AU - Salonen, Jarno

AU - Hirvonen, Jouni

AU - Elofsson, Mikael

AU - Sandler, Niklas

AU - Vuorela, Pia M

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N2 - Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.

AB - Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.

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Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.

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