The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance.

We developed an experimental model for studying the physicochemical basis of the adjuvant activity of surface-active agents. Pluronic polyols are chemically similar but physicochemically diverse surface-active agents composed of polymers of hydrophilic polyoxyethylene and lipophilic polyoxypropylene. One of them, L121, was found to be a powerful adjuvant for increasing antibody formation to BSA in mice when injected in an oil-in-water emulsion. Another, L101, was less effective in increasing antibody formation, but was more effective in inducing granulomatous inflammation. Three others had little effect on either response. The ability of these and other surface active agents to serve as adjuvants correlated with a physicochemical parameter, the hydrophile-lipophile balance (HLB). All of the surfactants with strong adjuvant activity have HLB values of less than 2. They are strongly lipophilic and promote the retention of macromolecules by oil drops in oil-in-water emulsions. We propose that the adjuvant activity of these compounds is dependent on their ability to concentrate the adjuvant, immunogen, and host proteins on hydrophobic surfaces, where they are more effectively presented to cells of the immune system.