Incorporation and release of cloxacillin sodium in micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide)

A novel drug carrier system was constructed from anionic drug cloxacillin sodium (CLX) and micelle of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) by incorporating the former into the micelle of the latter. The incorporation of CLX into the micelle of PS-PVP-PEO was confirmed by zeta-potential measurements, dynamic light scattering (DLS), and fluorescence spectroscopy. In the absence of the anionic drug, CLX, the zeta-potential of neat PS-PVP-PEO micelle was + 13 mV under aqueous acidic condition due to the presence of positive charges in the PVP unit. The addition of CLX into the micelle of PS-PVP-PEO decreased the zeta-potential of the micelle smoothly and finally led to a minimum zeta-potential around 0 mV. This fact shows that the added CLX is effectively incorporated into the PS-PVP-PEO micelle by electrostatic attraction. In concomitant with the decrease in zeta-potential, a decrease in hydrodynamic diameter from 94 to 69 nm was observed on addition of CLX to the PS-PVP-PEO micellar solution. This fact also indicates the incorporation of CLX into the PS-PVP-PEO micelles because the binding of CLX to the PVP block of the micelles induces a conformational change from an extended to a shrunken form due to the cancellation of the repulsive force in the PVP blocks by CLX. Fluorescence quenching of pyrene by CLX gave additional evidence for the effective bindings of CLX to the PS-PVP-PEO micelles. Further, release of CLX from the nanoaggregates of CLX/PS-PVP-PEO was investigated in vitro. It was found that the release kinetics of the CLX is conformed to a model based on the consecutive chemical kinetics.