Etoposide (VP-16) uptake by tumour spheroids and activity in the presence of Brij 30, formulation additives and sodium salicylate.

A number of additives typically used in the formulation of poorly soluble drugs can be shown to influence drug transport across various physiological barriers. Multicellular spheroids from a human neuroblastoma cell line (NB1-G) were used to investigate the effect of etoposide in solution, as its commercial formulation, Vepesid, in the presence of a nonionic surfactant, Brij 30, and a hydrotropic agent, sodium salicylate. Enhanced growth delay, apparently related to increased drug uptake, was observed both with the Vepesid and the sodium salicylate formulations. Brij 30, however, showed no enhancement of growth delay or drug uptake at a concentration at which it was not in itself cytotoxic. Significant morphological changes in the spheroid were observed at higher concentrations of additives, particularly with Brij 30, emphasizing the fact that many formulation additives cannot be used with impunity in tissue culture systems. The enhanced uptake of drug into tumour cells and potential synergy between additive and drug is worthy of further investigation.