Bacteriophages may be formulated into semi‐solid bases for therapeutic delivery. This work investigated the effects of a range of preservatives on the viability of Myoviridae and Siphoviridae bacteriophages when these were formulated into a standard semi‐solid cream base. The six preservatives tested included: benzoic acid (0·1%), chlorocresol (0·1%), combination hydroxybenzoates (propyl 4‐hydroxybenzoates with methyl 4‐hydroxybenzoates) (0·1%), methyl 4‐hydroxybenzoate (0·08%), 2‐phenoxyethanol (1%) and propyl 4‐hydroxybenzoate (0·02%). These were each formulated into cetomacrogol cream aqueous to generate six individual semi‐solid bases into which Myoviridae and Siphoviridae bacteriophages were added and tested for stability. Optimal bacteriophage stability was seen when the preservative chlorocresol was used. Bacteriophage in the acidic benzoic acid were the least stable, resulting in complete loss of viability after 4–5 weeks. Of the bacteriophages tested, the Myoviridae KOX1 was significantly more stable than the Siphoviridae PAC1 after 91 days in formulations with each of the preservatives. Our results suggest the need for individual testing of specific bacteriophages in pharmaceutical formulations, as their efficacy when exposed to preservatives and excipients in these delivery forms may vary.

中文翻译：

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一系列防腐剂对半固体乳膏制剂中的肌病毒科和虹吸病毒科噬菌体的不同影响

噬菌体可以配制成半固体基质用于治疗。这项工作研究了一系列防腐剂对 Myoviridae 和 Siphoviridae 噬菌体活力的影响，当它们被配制成标准的半固体乳膏基质时。测试的六种防腐剂包括：苯甲酸 (0·1%)、氯甲酚 (0·1%)、组合羟基苯甲酸酯（4-羟基苯甲酸丙酯和 4-羟基苯甲酸甲酯）（0·1%）、4-羟基苯甲酸甲酯（0· 08%)、2-苯氧基乙醇 (1%) 和 4-羟基苯甲酸丙酯 (0·02%)。将它们分别配制成西托聚醇乳膏水溶液，以产生六种单独的半固体基质，其中加入肌病毒科和虹吸病毒科的噬菌体并测试稳定性。当使用防腐剂氯甲酚时，可以看到最佳的噬菌体稳定性。酸性苯甲酸中的噬菌体最不稳定，导致 4-5 周后完全丧失活力。在测试的噬菌体中，在含有每种防腐剂的制剂中，在 91 天后，肌病毒科 KOX1 明显比丝裂病毒科 PAC1 更稳定。我们的结果表明需要对药物制剂中的特定噬菌体进行单独测试，因为它们在暴露于这些递送形式中的防腐剂和赋形剂时的功效可能会有所不同。