TY - JOUR AU - Sun, Hsien-Kuo AU - Seshadri, Madhumathi AU - Lingard, Scott AU - Monaghan, Wayne AU - Faoagali, Joan AU - Chan, Enoch AU - McDonald, Helen AU - Houston, Todd AU - King, Michelle AU - Peak, Ian AU - Wilson, Jennifer C. AU - Haywood, Alison AU - Spencer, Briohny AU - Dunn, Perrea AU - Grant, Gary Dean PY - 2011 TI - Antibacterial Activity of β-Cyclodextrin and 2-Hydroxypropyl-β-Cyclodextrin Trimethoprim Complexes JF - Current Research in Microbiology VL - 2 IS - 1 DO - 10.3844/ajmsp.2011.1.8 UR - https://thescipub.com/abstract/ajmsp.2011.1.8 AB - 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: β-cyclodextrin and 2-hydroxypropyl β-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 β-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-β-cyclodextrin and β-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.