Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation

Abstract

Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery.

Novel Intranasal Drug Delivery: Geraniol Charged Polymeric Mixed Micelles for Targeting Cerebral Insult as a Result of Ischaemia/Reperfusion

“…These peaks correspond to O-H and C=C, respectively. In the plain formula, several peaks can be distinguished at 3500, 1750, and 1107 cm −1 owing to O-H, C=O, and C-H groups, respectively, which are corresponding to the formula components main active groups of Cremophor EL and Pluronic F127 [59,60]. In the case of geraniol polymeric mixed micelles formula (F3), changes of absorption bands intensities and peak shift at 3372, 2973, 2669, and 980 cm −1 can be easily distinguished.…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…Liu et al synthesized α-tocopherol (TOC) conjugated with F127 polymer (F127-SS-TOC) through a redox-sensitive disulfide bond between F127 and TOC. These F127-SS-TOC micelles showed high hemocompatibility and low cytotoxicity in Bel 7402 and L02 cells (Liu, Fu, et al, 2017). …”

Preparation, characterization and anticancer activities of resveratrol loaded redox-sensitive F127-SS-TOC micelles

“…RES loaded F127-SS-TOC (F127-SS-TOC/RES) micelles were prepared using the solvent evaporation method as reported previously. 17 Briey, 10 mg F127-SS-TOC polymer and 2 mg RES were completely dissolved in 1 mL methanol. Then obtained organic solution was added drop-wise into 10 mL distilled water under vigorous stirring for 6 h at room temperature in the dark.…”

“…15,16 In our previous study, we synthesized a redox-sensitive Pluronic F127-SS-a-tocopherol (TOC) polymer using a disulde bond to link F127 and TOC, which might cleave in response to reductive environment of intracellular GSH in cancer cells. 17 Resveratrol (RES), a natural antioxidant polyphenolic compound, is found in a variety of plants, including grapes, berriers, peanuts, the roots of Polygonum, et al [18][19][20] Besides, it was reported that due to the structure similarity between RES and estrogenic agent diethylstilbestrol, RES could be a phytoestrogen. 1 RES, the main ingredient of red wine, had potential in inhibiting the growth of different types of cancer without obvious side effects.…”