The biological activity of phenolic compounds. The effect of surface active substances upon the penetration of hexyl resorcinol into Ascaris lumbricoides var. suis

Abstract

The effect of surface active substances (sodium cholate, sodium oleate and cetyl trimethyl ammonium bromide (C.T.A.B.)), upon the penetration of hexyl resorcinol into the pig roundworm (Ascaris lumbricoides var. suis) has been measured quantitatively, and parallel measurements carried out upon the interfacial activity of these solutions against an inert mineral oil. In all three cases a marked similarity of action, differing only in degree, was observed. Using a fixed hexyl resorcinol concentration (0.025%) the soap in dilute solution accelerated the penetration of this drug, the maximum accelerations being in the order sodium $\text{cholate}$ $\ll $ $\text{sodium oleate}$ $<\text{C.T.A.B.}$, but when present in high concentration the penetration was completely inhibited. The soaps alone were found to penetrate Ascaris very slowly, if at all, the amounts taken up being reasonably explained on the basis of surface adsorption only. Measurement of interfacial tensions showed that the soap and hexyl resorcinol molecules associate at an interface, forming a labile complex of increased surface activity. Using a fixed drug concentration (0.025% as above), the interfacial tension went through a minimum as the soap concentration was increased, ultimately rising to the value for the soap alone. Maximum interfacial activity (i.e. minimum interfacial tension), was found in all cases to occur at that soap concentration giving maximum hexyl resorcinol penetration into Ascaris, and was in the same order, viz. $\text{cholate}$ $\ll $ $\text{oleate}<\text{C.T.A.B.}$ The interfacial tension measurements also showed that this particular soap concentration corresponded to the onset of micellar aggregation of the soap molecules. From the interfacial tension data a simple explanation for the biological measurements can be suggested, which at the same time appears to explain a number of observations upon other biological systems, in particular the effect of soaps upon the bactericidal activity of phenols. This explanation suggests that the biological activity of hexyl resorcinol (as measured by its rate of penetration) is determined by the interfacial activity of the mixture, and that when soap micelles are present the drug distributes itself between the micelles and any other interface present (e.g. oil/water or Ascaris/water). The maximum biological activity thus occurs at the critical concentration for micelle formation, since this has maximum interfacial activity. At high soap concentrations the hexyl resorcinol is mainly held by the soap micelles, so that the biological activity is thereby diminished, ultimately to zero since the soaps alone penetrate so extremely slowly. In the case of C.T.A.B./hexyl resorcinol mixtures it has been possible, from physical data only, to calculate a theoretical curve for the biological activity which is in good agreement with experiment. The possible bearings of these conclusions upon in vivo activity of hexyl resorcinol as an anthelmintic, and upon drug action in general, are briefly mentioned.