Selecting surfactants for the maximum inhibition of the activity of the multidrug resistance efflux pump transporter, P-glycoprotein: conceptual development.

Amphiphilic excipients, such as surfactants, have been shown to be inhibitors of the multidrug resistance (MDR) efflux pump transporter protein, P-glycoprotein (Pgp). In vitro studies using manysurfactants have demonstrated that those with an optimum hydrophilic-lipophilic balance (HLB) exhibit greater efflux pump inhibition than those that are either very hydrophobic, or very hydrophilic, although the correlation of HLB to Pgp inhibition activity remains weak. Using the data from multiple in vitro studies, a model has been conceptualized that underscores the attributes of both the HLB and the critical micellar concentration (CMC), occurring in tandem, and unable of being varied independently, as key determinants toward prediction of surfactant Pgp inhibition activity. The algorithm that formalizes this concept provides a ‘semi-rational’ method of choosingsurfactants for a specific type of cancer for maximum inhibition of MDR.