Therapeutic applications of coenzyme Q10 (CoQ10) are greatly limited by its lack of solubility in aqueous media. In this study, polyethylene glycol monostearate (stPEG) was used to construct micelles containing CoQ10 as a new formulation. The micellar formulations (stPEG/CoQ10) were prepared using five types of stPEG with 10, 25, 40, 55, and 140 PEG repeat units, respectively. The micellar preparation was simple, consisting of only stPEG and CoQ10. Next, we compared the physical properties and blood circulation of these micelles. The CoQ10 load of this formulation was approximately 15 w/w%. Based on the dynamic light scattering method, the average molecular size of the stPEG/CoQ10 micelles was approximately 15 to 60 nm. The zeta potentials of these micelles were approximately −10 to −25 mV. The micelles using stPEG25, 40, and 55 demonstrated high solubility in water. Furthermore, these micelles had in vitro antioxidant activity. On comparing the blood circulation of micelles using stPEG25, 40, 55, and 140, micelles using stPEG55 had a significantly higher circulation in blood. The stPEG55/CoQ10 micelle demonstrated a protective effect against acetaminophen-induced liver injury in mice. In conclusion, these data indicate that the intravenous administration of the stPEG/CoQ10 micellar aqueous formulation is of great value against oxidant stress.

Macromolecular conjugates of mitomycin C (MMC) were synthesized by binding an active ester of glutarylated MMC (MMC-G-OSu) to human holo-transferrin (TF). Water-soluble TF-MMC conjugates (TF-G-MMC) were obtained in a good yield (> 95%) by this method. The MMC content of the conjugate increased (0.82-9.49 MMC/w%) with increasing amounts of MMC-G-OSu added to the conjugation mixture. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed no aggregation in these conjugates. 125I-TF-G-MMC was bound specifically to the TF receptor on Sarcoma 180 cells; the measurement of equilibrium binding of the 125I-labeled conjugate resulted in a saturation isotherm. The amount of conjugate specifically bound to the TF receptor decreased as the MMC content of the conjugate increased. However, it was found that the conjugate with an MMC content below 10 mol MMC/mol TF still retains a binding activity of more than half that of TF. Therefore, when an optimal chemical modification was chosen, TF could be used as a tumor specific drug carrier.

Background/Objectives: Trans-resveratrol (Res) has been reported to possess many biological activities, including neuroprotective effects, owing to its anti-inflammatory and antioxidant properties. However, Res has very low water solubility, which limits its therapeutic application. In this work, we formulated water-soluble micellar formulations incorporating Res using polyethylene glycol monostearate (stPEG). Methods: These formulations (stPEG/Res) were developed using five types of stPEG containing 10, 25, 40, 55 and 140 PEG repeat units. The formulations were characterized for Res content, water solubility, particle size, zeta potential, precipitation, biodistribution, and efficacy against neuronal and motor dysfunction in intracerebral hemorrhage (ICH). Results: Intravenous administration of stPEG40/Res, which demonstrated particle size, water solubility, and biodistribution properties suitable for intravenous administration, suppressed neurological and motor dysfunction following in a collagenase-induced ICH mouse model. These effects were inhibited by zinc protoporphyrin-9, an inhibitor of the antioxidant enzyme heme oxygenase-1, suggesting that Res contributes to antioxidant enzyme expression and anti-inflammatory activity. Conclusions: The stPEG/Res micellar formulation developed in this study may offer a promising therapeutic approach for ICH treatment.