Studies of the effect of anesthetic molecules, halothane and isoflurane, on the aggregation behavior of POE-POP-POE triblock copolymers, P84, F88, P104, in aqueous solution have been carried out using fluorescence spectroscopy and light-scattering techniques. The hydrodynamic radius of block copolymer aggregates and the I/III vibronic intensity ratio of pyrene in 5 wt % aqueous solutions of F88, P84, and P104 were obtained over a wide temperature range, 10-60 °C. Large-sized clusters form at low temperatures for P104, but they do not have a well-defined hydrophobic core. Low concentrations of the anesthetics are found to induce the aggregation of F88 and P84 at 25 °C, and this effect is similar to that of increasing the temperature. The effect of halothane and isoflurane concentration on the change of hydrodynamic radius of copolymer aggregates and the I/III vibronic ratio of pyrene in F88, P84, and P104 were investigated at 25 °C. The addition of 1 mM of anesthetic is equivalent to ca. a 1-2 °C increase in temperature. It is deduced that the anesthetic molecules are distributed in both the hydrophobic core and hydrophilic corona of the polymer micelles. However, whereas an increase in temperature removes water of hydration from around the POP and POE segments, the anesthetic molecules tend to replace water of hydration around these segments. It is inferred that anesthetic molecules could disturb the water of hydration around biological macromolecules, and it is proposed that the dehydration effect of inhalation anesthetics may play an important role in the process of anesthesia.

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The potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers and oral drug delivery system was well known. Herein, we investigated the possibility of PAMAM dendrimers for promoting the solubility and oral bioavailability of puerarin. In the present study, the effect of PAMAM dendrimers with different generations (G1.5, G2, G2.5, and G3) on the solubility of puerarin was evaluated at different concentrations and pH conditions. Further more, the puerarin-G2 dendrimer complex was conducted for the in vitro hemolytic toxicity studies and pharmacokinetics studies in rats. The solubility of puerarin was significantly higher in the presence of the full generation dendrimers (e.g. G2 and G3). No significant hemolysis was observed on erythrocytes (G2, 0-2.5 mg/mL) in the hemolytic toxicity studies. The pharmacokinetics parameters Tmax, Cmax, and AUC0-8 h of puerarin suspension solution and puerarin-G2 dendrimer complex solution were 0.76 h, 1.50 µg/mL, 7.33 µg·h/mL and 0.33 h, 6.49 µg/mL, 14.02 µg·h/mL, respectively. These studies demonstrate that PAMAM dendrimers may be a promising strategy for peroral delivery of puerarin.

Time-resolved fluorescence quenching of excited state pyrene by halothane was investigated in aqueous solutions of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock copolymers, P84, P104, and F38, at 25°C. The occupancy number of halothane in the block copolymer micelles and the dispersive factor were obtained from nonlinear least-squares fitting of the immobile quencher-probe and dispersive kinetic models, respectively. It is shown that these parameters depend on the concentration of halothane in the system and the hydrophobic/hydrophilic balance of the block copolymers. The application of dispersive kinetics appears to be a suitable technique to investigate the self-aggregation behavior of self-assembly systems. Exponential series lifetime-distribution analysis was also carried out and the results support the presence of aggregates of triblock copolymers in these systems. The results of this study suggest that halothane molecules distribute primarily in the core of the micelles but, upon saturation of the core, begin to locate in the corona of the block copolymer aggregates.