Treatment of human cytomegalovirus (CMV) infection requires long-term administration of nucleoside analog antivirals such as ganciclovir (GCV), a therapy frequently limited by GCV-induced toxicity. Here, combining GCV treatment with two bioactive excipients, poloxamer 188 and quercetin, was investigated in vitro to reduce GCV dosage. Quercetin is a natural flavonoid exhibiting antiviral activity against CMV by a mechanism distinct from GCV, but is poorly soluble, limiting its use as a therapeutic. To overcome this challenge, quercetin was co-formulated with poloxamer 188 (P188, Pluronic ® F68). Quercetin-P188 (QP188) formulations yielded only modest CMV viral inhibition, with a selectivity index of 11.4, contrasted with a GCV selectivity index of 95. More significantly, when coadministered with GCV, QP188 exhibited an additive or synergistic interaction in subtherapeutic ranges of GCV. Fluorescence microscopy revealed QP188 accumulation in fibroblast mitochondria, suggesting that the excipient may modulate mitochondrial processes relevant to CMV infection. GCV antiviral therapy augmented with poloxamer-solubilized quercetin may be a viable approach to maintain CMV inhibition while lowering GCV doses, translating to reduced associated toxicity.
Keywords: Cytomegalovirus; Excipients; Ganciclovir; Poloxamer 188; Quercetin.
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