Resveratrol-loaded PLGA nanoparticles functionalized with red blood cell membranes as a biomimetic delivery system for prolonged circulation time

摘要

Resveratrol (RES) shows excellent pharmacological activities but is limited by a very short half-life. In this study, red blood cell (RBC) membranes camouflaging RES-loaded PLGA NPs (RBC-RES-NPs) were successfully designed and synthesized. The resulting RBC-RES-NPs were spherical and had a clear core-shell structure with an average size of 148.1 +/- 1.1 nm and a negatively charged surface of -18.20 +/- 0.73 mV. The entrapment efficiency and drug loading rate were 96.51 +/- 1.29% and 1.79 +/- 0.02%, respectively. The diameter and distribution of the RBC-RES-NPs were largely stable for 7 consecutive days. Compared with that of RES and the RES-NPs, a remarkably sustained release effect was observed in the RBC-RES-NP group, with a cumulative release rate of approximately 60% after 2 h of measurement time. After systemic injection in rats, the half-life of the RBC-RESNPs (10.34 +/- 1.40 min) was distinctly longer than that of RES (7.50 +/- 1.00 min, p < 0.01) and the RES-NPs (7.31 +/- 1.37 min, p < 0.01). Additionally, the mean residence time of the RBC-RES-NPs was significantly extended. These results suggest that functionalization with RBC membranes as a biomimetic delivery system represents an efficient strategy to prolong the circulation time of RES, which may lead to an increase in the therapeutic effect of RES.