The toxic effect of solubilizing excipients on Tetrahymena thermophila BF5 growth investigated by microcalorimetry

Abstract

The toxic effect of different solubilizing excipients on the growth and metabolism of Tetrahymena thermophila BF 5 (T.t.BF 5 ) at various concentrations was investigated by microcalorimetry. The thermogenic curves of T.t.BF 5 growth were determined at 28°C, and were evaluated by dynamic parameters. The results indicated that the values of growth rate constant (k), maximum power (P 1 , P 2 ), peak time (T 1 , T 2 ) and total quantity of heat (Q) varied for different excipients. There was a good linear relationship between k and concentrations (r>0.95, P<0.01). 5% inhibition concentration (IC 5 ) of poloxamer 188, Tween 80, PEG 600, PEG 400 and Tween 20 was 2.18, 1.07, 1.35, 0.58, and 0.045 mg/mL, respectively. After the principal component analysis (PCA), Q, k and P 1 could characterize the effect of these excipients on T.t.BF 5 growth. Comprehensive evaluation indicated that compared with the control group, poloxamer 188 had the weakest toxicity and Tween 20 had the strongest toxicity. solubilizing excipients, Tetrahymena thermophila BF 5 , microcalorimetry, IC 5 , PCA Citation: Zhang S F, Yan D, Tang H Y, et al. The toxic effect of solubilizing excipients on Tetrahymena thermophila BF 5 growth investigated by microcalorimetry.As nonionics, the structure of solubilizing excipients includes not only hydrophilic groupings, but also lipophilic groupings to form micelles or reverse micelles in the solution. Therefore, the solubilizing excipients could be used in the indissolvable liquid preparation as solubilizers or emulsifiers [1]. However, different biologic toxicities are possibly produced due to the excipient itself or the byproduct such as the ekibon, ethylene alcohol, and diethylene glycol. The security problems of the excipients, especially applied to the injection, seem to be serious. The general evaluation methods supply direct and apparent results for security evaluation of the solubilizing excipients [2], but shortcomings such as strong subjectivity and less sensitivity make the evaluation hard to be objective and quantifiable. It is necessary to develop an objective and sensitive method to evaluate biological security of the solubilizing excipients.T.t.BF 5 is a type of eukaryotic protozoa living in the fresh water which solely contains one cell. It has a representative subcellular structure which is seen among most of the eucaryons. It has similarities with cells of higher animals [3]. It contacts the outside environment through cellular membranes without cell walls. This cellular membrane could response more rapidly to the change of the outside environment than higher animals [4]. Because its growth curve corresponds with the representative growth curve of microbes, the reaction of T.t.BF 5 to the surrounding toxicant could be studied by analyzing the dynamic thermal growth curves.T.t.BF 5 has been applied in the fields of biology, pharmacy, toxicology, environment and polluted water evaluation as a perfect model [5][6][7][8][9]. However, few reports showed that it was applied to evaluate the toxicity ...

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