Assessing Resveratrol Phuronic F 127 Micelle Stability in the Presence of Plasma Proteins Using Fluorescence Resonance Energy Transfer (FRET)
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Resveratrol (RES) is a polyphenolic compound with potential for chemopreventative and chemotherapeutic uses. However, exploration has been hindered by its short biologic half-life of ~6 minutes. Using polymeric micelles composed of Pluronic® F 127 may be a way to enhance the in vivo half-life of RES. Our objective is to investigate the in vitro stability of RES-5 mg/ml F127 formulation using FRET. DiI and DiO were used as the FRET fluorophore pair & incorporated into the micelle. In an intact micelle, no loss of signal is seen. However, when the system destabilizes, loss of signal is noted. The FRET pair was excited at 484 nm & emission was detected at 505 nm (DiO) & 570 nm (DiI). In vitro stability of micelles with and without RES was evaluated in the absence and presence of plasma proteins: albumin, α-β- and γ-globulins. F 127 micelles without RES were destabilized in the presence of plasma proteins in a statistically significant manner over a two hour time period. F127 micelles with RES are destabilized primarily by dilution. These micelles are re-stabilized in the presence of plasma proteins in a statistically significant manner, however the stabilization does not lead to complete recovery of micelle stability as compared to F127 micelles without RES. Based on these findings, F 127- RES formulation is more susceptible to dilution than plasma protein based destabilization. Further study in an in vivo model must be explored to validate the in vitro findings.
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