Antibacterial Activity of b-Cyclodextrin and 2-Hydroxypropyl-b-Cyclodextrin Trimethoprim Complexes

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Title Antibacterial Activity of b-Cyclodextrin and 2-Hydroxypropyl-b-Cyclodextrin Trimethoprim Complexes
Author Sun, Hsien; Seshadri, Madhumathi; Lingard, Scott; Monaghan, Wayne; Faoagali, Joan; Chan, Enoch; McDonald, Helen Wendy; Houston, Todd Ashley; King, Michelle Annette; Peak, Ian; Wilson, Jenny; Haywood, Alison; Spencer, Briohny Hope; Dunn, Perrea; Grant, Gary Dean
Journal Name American Journal of Microbiology
Year Published 2011
Place of publication United States
Publisher Science Publications
Abstract Abstract: Problem statement: Cyclodextrin complexation has previously been shown to improve the solubility and dissolution properties of trimethoprim; however, no report provides an account of the effect cyclodextrin complexation has on the antibacterial activity of this agent. Approach: b-cyclodextrin and 2-hydroxypropyl b-cyclodextrin inclusion complexes of trimethoprim were prepared and confirmed by differential scanning calorimetry and proton nuclear magnetic resonance. The in-vitro antibacterial activity, in terms of minimum inhibitory concentrations, of cyclodextrin-drug complexes were compared to uncomplexed free trimethoprim by a broth-microdilution method against several sensitive and resistant Gram-positive and Gram-negative bacteria. The effect of complexation on the apparent permeability coefficients was also determined using a Caco-2 permeability assay to account for potential alterations in bioavailability that could influence in-vivo antibacterial activity. Results: Inclusion complexation of trimethoprim with both unsubstituted and hydroxylated versions of b-cyclodextrin produced a reduction in the MIC80 required to inhibit the growth of S. aureus ATCC 29213, S. pneumoniae ATCC 4961, S.epidermidis ATCC 14990 and E. coli ATCC 25922 (p>0.05). The effect was limited to bacteria normally susceptible to trimethoprim. Neither complex negatively affected the antibacterial activity of trimethoprim. Hydroxypropyl-b-cyclodextrin and b-cyclodextrin inclusion complexes significantly (p<0.01) increased the apparent intestinal permeability of trimethoprim by 39.8 and 56.1%, respectively. Considering the effect cyclodextrin inclusion complexation has on the antibacterial activity of trimethoprim, the improved intestinal permeability of these complexes has the potential to improve the in-vivo antibacterial activity of the agent by enhancing the steady-state concentration of the drug when dosed orally. Conclusion: These results would suggest that physical complexation with either of these cyclodextrins would provide a feasible strategy to improve the pharmaceutical and pharmacokinetic properties of trimethoprim.
Peer Reviewed Yes
Published Yes
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Copyright Statement Copyright remains with the authors 2011. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this journal please refer to the journal’s website or contact the authors.
Volume 2
Issue Number 1
Page from 1
Page to 8
ISSN 1948-982X
Date Accessioned 2012-01-19
Language en_US
Research Centre Institute for Glycomics; Population and Social Health Research Program; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Biological Sciences
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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